Integrative Family Medicine
Leigh Ann Chapman ND
Leigh Ann Chapman ND
1567 SE Tacoma Street Portland OR 97202
ph 5032338113
wwwSellwoodFamilyMedicinecom
ABSTRACT
The CDC has announced that autism is the fastest growing developmental disability in the United States
With this staggering increase in diagnoses all primary care providers must be poised to evaluate and treat
children and adults with autism spectrum disorders This presentation will review the most up to date diagnostic
criteria research and treatments for patients with autism spectrum disorders
CDC reports autism is 1 in 88
1 in 88 translates to 1 in 54 boys and 1 in 252 girls
23 increase compared to 2006 (1 in 110)
78 increase compared to 2002 (1 in 150)
2008 surveillance year covered a total population of 337093 children aged 8 years
What about state by state statistics
MMWR Surveill Summ 2012 Mar 3061(3)1-19
South Korea- 1 in 38 Prevalence of autism spectrum disorders in a total
population sample Kim YS Leventhal BL Koh YJ Fombonne
E Laska E Lim EC Cheon KA Kim SJ Kim YK Lee H Song DH Grinker
RR Am J Psychiatry 2011 Sep168(9)904-12
Population screening and direct assessment
264 of children in a South Korean community in 2006 have and ASD
What does this mean
Risk Factors and Characteristics- endorsed by the CDC Identical twins if one child has an ASD then the other will be affected
about 36-95 of the time Parents who have a child with an ASD have a 2ndash18 chance of having
a second child who is also affected ASDs tend to occur more often in people who have certain genetic or
chromosomal conditions About 10 of children with autism are also identified as having Down syndrome fragile X syndrome tuberous sclerosis and other genetic and chromosomal disorders
The majority (62) of children with ASDs did not have intellectual disability
Children born to older parents are at a higher risk for ASDs A small percentage of children who are born prematurely or with low
birth weight are at greater risk for having ASDs ASD commonly co-occurs with other developmental psychiatric
neurologic chromosomal and genetic diagnoses
Autism Diagnostic criteria New and improved as of May 2013
The DSM-5 manual is the only location for diagnostic criteria for Autism
This is a psychiatric manual and does not account for the evolution of biological whole systems medicine
DSM 5 - Change 1 Elimination of subcategories of
Asperger syndrome
PDD-NOS
childhood disintegrative disorder
autistic disorder
All of these subcategories are folded into the broad term autism spectrum disorder (ASD)
DSM-5 change 2 DSM-4- three domains of impairment
social impairment
languagecommunication impairment
repetitiverestricted behaviors
DSM-5- Two categories social communication impairment
restricted interestsrepetitive behaviors
New symptom will be included hyper- or hypo-reactivity to sensory input or unusual
interests in sensory aspects of the environment
Sensory Processing
ldquoIt is obvioushellipthat sensory processing abnormalities in ASD are distributed rather than localized sensory abnormalities in ASD obviously span multiple dimensions of latency adaptation magnitude and behavior abnormalities with both enhanced and impaired behavior associated with aberrant cortical responses Given this diversity in findings the heterogeneity of ASD and broad variability seen over and over again in the ASD groups almost irrespective of the study it is hard to imagine that one single theory could account for all of these observationshellip It is therefore probable that several mechanisms and neuronal abnormalities most likely at multiple levels (from single neurons through to inter-area connections) all contribute to varying degrees to the abnormal sensory processing observed in ASD It is also likely that no single mechanism is unique to one sensory modality which is why we see such a widely distributed range of abnormalities across modalitiesrdquo Kenet T 2011 Sensory functions in ASD In The Neuropsychology of Autism edited by D Fein New York Oxford University Press
DSM 5 change 3 Each person evaluated will also be described in terms
of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
ABSTRACT
The CDC has announced that autism is the fastest growing developmental disability in the United States
With this staggering increase in diagnoses all primary care providers must be poised to evaluate and treat
children and adults with autism spectrum disorders This presentation will review the most up to date diagnostic
criteria research and treatments for patients with autism spectrum disorders
CDC reports autism is 1 in 88
1 in 88 translates to 1 in 54 boys and 1 in 252 girls
23 increase compared to 2006 (1 in 110)
78 increase compared to 2002 (1 in 150)
2008 surveillance year covered a total population of 337093 children aged 8 years
What about state by state statistics
MMWR Surveill Summ 2012 Mar 3061(3)1-19
South Korea- 1 in 38 Prevalence of autism spectrum disorders in a total
population sample Kim YS Leventhal BL Koh YJ Fombonne
E Laska E Lim EC Cheon KA Kim SJ Kim YK Lee H Song DH Grinker
RR Am J Psychiatry 2011 Sep168(9)904-12
Population screening and direct assessment
264 of children in a South Korean community in 2006 have and ASD
What does this mean
Risk Factors and Characteristics- endorsed by the CDC Identical twins if one child has an ASD then the other will be affected
about 36-95 of the time Parents who have a child with an ASD have a 2ndash18 chance of having
a second child who is also affected ASDs tend to occur more often in people who have certain genetic or
chromosomal conditions About 10 of children with autism are also identified as having Down syndrome fragile X syndrome tuberous sclerosis and other genetic and chromosomal disorders
The majority (62) of children with ASDs did not have intellectual disability
Children born to older parents are at a higher risk for ASDs A small percentage of children who are born prematurely or with low
birth weight are at greater risk for having ASDs ASD commonly co-occurs with other developmental psychiatric
neurologic chromosomal and genetic diagnoses
Autism Diagnostic criteria New and improved as of May 2013
The DSM-5 manual is the only location for diagnostic criteria for Autism
This is a psychiatric manual and does not account for the evolution of biological whole systems medicine
DSM 5 - Change 1 Elimination of subcategories of
Asperger syndrome
PDD-NOS
childhood disintegrative disorder
autistic disorder
All of these subcategories are folded into the broad term autism spectrum disorder (ASD)
DSM-5 change 2 DSM-4- three domains of impairment
social impairment
languagecommunication impairment
repetitiverestricted behaviors
DSM-5- Two categories social communication impairment
restricted interestsrepetitive behaviors
New symptom will be included hyper- or hypo-reactivity to sensory input or unusual
interests in sensory aspects of the environment
Sensory Processing
ldquoIt is obvioushellipthat sensory processing abnormalities in ASD are distributed rather than localized sensory abnormalities in ASD obviously span multiple dimensions of latency adaptation magnitude and behavior abnormalities with both enhanced and impaired behavior associated with aberrant cortical responses Given this diversity in findings the heterogeneity of ASD and broad variability seen over and over again in the ASD groups almost irrespective of the study it is hard to imagine that one single theory could account for all of these observationshellip It is therefore probable that several mechanisms and neuronal abnormalities most likely at multiple levels (from single neurons through to inter-area connections) all contribute to varying degrees to the abnormal sensory processing observed in ASD It is also likely that no single mechanism is unique to one sensory modality which is why we see such a widely distributed range of abnormalities across modalitiesrdquo Kenet T 2011 Sensory functions in ASD In The Neuropsychology of Autism edited by D Fein New York Oxford University Press
DSM 5 change 3 Each person evaluated will also be described in terms
of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
CDC reports autism is 1 in 88
1 in 88 translates to 1 in 54 boys and 1 in 252 girls
23 increase compared to 2006 (1 in 110)
78 increase compared to 2002 (1 in 150)
2008 surveillance year covered a total population of 337093 children aged 8 years
What about state by state statistics
MMWR Surveill Summ 2012 Mar 3061(3)1-19
South Korea- 1 in 38 Prevalence of autism spectrum disorders in a total
population sample Kim YS Leventhal BL Koh YJ Fombonne
E Laska E Lim EC Cheon KA Kim SJ Kim YK Lee H Song DH Grinker
RR Am J Psychiatry 2011 Sep168(9)904-12
Population screening and direct assessment
264 of children in a South Korean community in 2006 have and ASD
What does this mean
Risk Factors and Characteristics- endorsed by the CDC Identical twins if one child has an ASD then the other will be affected
about 36-95 of the time Parents who have a child with an ASD have a 2ndash18 chance of having
a second child who is also affected ASDs tend to occur more often in people who have certain genetic or
chromosomal conditions About 10 of children with autism are also identified as having Down syndrome fragile X syndrome tuberous sclerosis and other genetic and chromosomal disorders
The majority (62) of children with ASDs did not have intellectual disability
Children born to older parents are at a higher risk for ASDs A small percentage of children who are born prematurely or with low
birth weight are at greater risk for having ASDs ASD commonly co-occurs with other developmental psychiatric
neurologic chromosomal and genetic diagnoses
Autism Diagnostic criteria New and improved as of May 2013
The DSM-5 manual is the only location for diagnostic criteria for Autism
This is a psychiatric manual and does not account for the evolution of biological whole systems medicine
DSM 5 - Change 1 Elimination of subcategories of
Asperger syndrome
PDD-NOS
childhood disintegrative disorder
autistic disorder
All of these subcategories are folded into the broad term autism spectrum disorder (ASD)
DSM-5 change 2 DSM-4- three domains of impairment
social impairment
languagecommunication impairment
repetitiverestricted behaviors
DSM-5- Two categories social communication impairment
restricted interestsrepetitive behaviors
New symptom will be included hyper- or hypo-reactivity to sensory input or unusual
interests in sensory aspects of the environment
Sensory Processing
ldquoIt is obvioushellipthat sensory processing abnormalities in ASD are distributed rather than localized sensory abnormalities in ASD obviously span multiple dimensions of latency adaptation magnitude and behavior abnormalities with both enhanced and impaired behavior associated with aberrant cortical responses Given this diversity in findings the heterogeneity of ASD and broad variability seen over and over again in the ASD groups almost irrespective of the study it is hard to imagine that one single theory could account for all of these observationshellip It is therefore probable that several mechanisms and neuronal abnormalities most likely at multiple levels (from single neurons through to inter-area connections) all contribute to varying degrees to the abnormal sensory processing observed in ASD It is also likely that no single mechanism is unique to one sensory modality which is why we see such a widely distributed range of abnormalities across modalitiesrdquo Kenet T 2011 Sensory functions in ASD In The Neuropsychology of Autism edited by D Fein New York Oxford University Press
DSM 5 change 3 Each person evaluated will also be described in terms
of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
South Korea- 1 in 38 Prevalence of autism spectrum disorders in a total
population sample Kim YS Leventhal BL Koh YJ Fombonne
E Laska E Lim EC Cheon KA Kim SJ Kim YK Lee H Song DH Grinker
RR Am J Psychiatry 2011 Sep168(9)904-12
Population screening and direct assessment
264 of children in a South Korean community in 2006 have and ASD
What does this mean
Risk Factors and Characteristics- endorsed by the CDC Identical twins if one child has an ASD then the other will be affected
about 36-95 of the time Parents who have a child with an ASD have a 2ndash18 chance of having
a second child who is also affected ASDs tend to occur more often in people who have certain genetic or
chromosomal conditions About 10 of children with autism are also identified as having Down syndrome fragile X syndrome tuberous sclerosis and other genetic and chromosomal disorders
The majority (62) of children with ASDs did not have intellectual disability
Children born to older parents are at a higher risk for ASDs A small percentage of children who are born prematurely or with low
birth weight are at greater risk for having ASDs ASD commonly co-occurs with other developmental psychiatric
neurologic chromosomal and genetic diagnoses
Autism Diagnostic criteria New and improved as of May 2013
The DSM-5 manual is the only location for diagnostic criteria for Autism
This is a psychiatric manual and does not account for the evolution of biological whole systems medicine
DSM 5 - Change 1 Elimination of subcategories of
Asperger syndrome
PDD-NOS
childhood disintegrative disorder
autistic disorder
All of these subcategories are folded into the broad term autism spectrum disorder (ASD)
DSM-5 change 2 DSM-4- three domains of impairment
social impairment
languagecommunication impairment
repetitiverestricted behaviors
DSM-5- Two categories social communication impairment
restricted interestsrepetitive behaviors
New symptom will be included hyper- or hypo-reactivity to sensory input or unusual
interests in sensory aspects of the environment
Sensory Processing
ldquoIt is obvioushellipthat sensory processing abnormalities in ASD are distributed rather than localized sensory abnormalities in ASD obviously span multiple dimensions of latency adaptation magnitude and behavior abnormalities with both enhanced and impaired behavior associated with aberrant cortical responses Given this diversity in findings the heterogeneity of ASD and broad variability seen over and over again in the ASD groups almost irrespective of the study it is hard to imagine that one single theory could account for all of these observationshellip It is therefore probable that several mechanisms and neuronal abnormalities most likely at multiple levels (from single neurons through to inter-area connections) all contribute to varying degrees to the abnormal sensory processing observed in ASD It is also likely that no single mechanism is unique to one sensory modality which is why we see such a widely distributed range of abnormalities across modalitiesrdquo Kenet T 2011 Sensory functions in ASD In The Neuropsychology of Autism edited by D Fein New York Oxford University Press
DSM 5 change 3 Each person evaluated will also be described in terms
of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Risk Factors and Characteristics- endorsed by the CDC Identical twins if one child has an ASD then the other will be affected
about 36-95 of the time Parents who have a child with an ASD have a 2ndash18 chance of having
a second child who is also affected ASDs tend to occur more often in people who have certain genetic or
chromosomal conditions About 10 of children with autism are also identified as having Down syndrome fragile X syndrome tuberous sclerosis and other genetic and chromosomal disorders
The majority (62) of children with ASDs did not have intellectual disability
Children born to older parents are at a higher risk for ASDs A small percentage of children who are born prematurely or with low
birth weight are at greater risk for having ASDs ASD commonly co-occurs with other developmental psychiatric
neurologic chromosomal and genetic diagnoses
Autism Diagnostic criteria New and improved as of May 2013
The DSM-5 manual is the only location for diagnostic criteria for Autism
This is a psychiatric manual and does not account for the evolution of biological whole systems medicine
DSM 5 - Change 1 Elimination of subcategories of
Asperger syndrome
PDD-NOS
childhood disintegrative disorder
autistic disorder
All of these subcategories are folded into the broad term autism spectrum disorder (ASD)
DSM-5 change 2 DSM-4- three domains of impairment
social impairment
languagecommunication impairment
repetitiverestricted behaviors
DSM-5- Two categories social communication impairment
restricted interestsrepetitive behaviors
New symptom will be included hyper- or hypo-reactivity to sensory input or unusual
interests in sensory aspects of the environment
Sensory Processing
ldquoIt is obvioushellipthat sensory processing abnormalities in ASD are distributed rather than localized sensory abnormalities in ASD obviously span multiple dimensions of latency adaptation magnitude and behavior abnormalities with both enhanced and impaired behavior associated with aberrant cortical responses Given this diversity in findings the heterogeneity of ASD and broad variability seen over and over again in the ASD groups almost irrespective of the study it is hard to imagine that one single theory could account for all of these observationshellip It is therefore probable that several mechanisms and neuronal abnormalities most likely at multiple levels (from single neurons through to inter-area connections) all contribute to varying degrees to the abnormal sensory processing observed in ASD It is also likely that no single mechanism is unique to one sensory modality which is why we see such a widely distributed range of abnormalities across modalitiesrdquo Kenet T 2011 Sensory functions in ASD In The Neuropsychology of Autism edited by D Fein New York Oxford University Press
DSM 5 change 3 Each person evaluated will also be described in terms
of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Autism Diagnostic criteria New and improved as of May 2013
The DSM-5 manual is the only location for diagnostic criteria for Autism
This is a psychiatric manual and does not account for the evolution of biological whole systems medicine
DSM 5 - Change 1 Elimination of subcategories of
Asperger syndrome
PDD-NOS
childhood disintegrative disorder
autistic disorder
All of these subcategories are folded into the broad term autism spectrum disorder (ASD)
DSM-5 change 2 DSM-4- three domains of impairment
social impairment
languagecommunication impairment
repetitiverestricted behaviors
DSM-5- Two categories social communication impairment
restricted interestsrepetitive behaviors
New symptom will be included hyper- or hypo-reactivity to sensory input or unusual
interests in sensory aspects of the environment
Sensory Processing
ldquoIt is obvioushellipthat sensory processing abnormalities in ASD are distributed rather than localized sensory abnormalities in ASD obviously span multiple dimensions of latency adaptation magnitude and behavior abnormalities with both enhanced and impaired behavior associated with aberrant cortical responses Given this diversity in findings the heterogeneity of ASD and broad variability seen over and over again in the ASD groups almost irrespective of the study it is hard to imagine that one single theory could account for all of these observationshellip It is therefore probable that several mechanisms and neuronal abnormalities most likely at multiple levels (from single neurons through to inter-area connections) all contribute to varying degrees to the abnormal sensory processing observed in ASD It is also likely that no single mechanism is unique to one sensory modality which is why we see such a widely distributed range of abnormalities across modalitiesrdquo Kenet T 2011 Sensory functions in ASD In The Neuropsychology of Autism edited by D Fein New York Oxford University Press
DSM 5 change 3 Each person evaluated will also be described in terms
of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
DSM 5 - Change 1 Elimination of subcategories of
Asperger syndrome
PDD-NOS
childhood disintegrative disorder
autistic disorder
All of these subcategories are folded into the broad term autism spectrum disorder (ASD)
DSM-5 change 2 DSM-4- three domains of impairment
social impairment
languagecommunication impairment
repetitiverestricted behaviors
DSM-5- Two categories social communication impairment
restricted interestsrepetitive behaviors
New symptom will be included hyper- or hypo-reactivity to sensory input or unusual
interests in sensory aspects of the environment
Sensory Processing
ldquoIt is obvioushellipthat sensory processing abnormalities in ASD are distributed rather than localized sensory abnormalities in ASD obviously span multiple dimensions of latency adaptation magnitude and behavior abnormalities with both enhanced and impaired behavior associated with aberrant cortical responses Given this diversity in findings the heterogeneity of ASD and broad variability seen over and over again in the ASD groups almost irrespective of the study it is hard to imagine that one single theory could account for all of these observationshellip It is therefore probable that several mechanisms and neuronal abnormalities most likely at multiple levels (from single neurons through to inter-area connections) all contribute to varying degrees to the abnormal sensory processing observed in ASD It is also likely that no single mechanism is unique to one sensory modality which is why we see such a widely distributed range of abnormalities across modalitiesrdquo Kenet T 2011 Sensory functions in ASD In The Neuropsychology of Autism edited by D Fein New York Oxford University Press
DSM 5 change 3 Each person evaluated will also be described in terms
of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
DSM-5 change 2 DSM-4- three domains of impairment
social impairment
languagecommunication impairment
repetitiverestricted behaviors
DSM-5- Two categories social communication impairment
restricted interestsrepetitive behaviors
New symptom will be included hyper- or hypo-reactivity to sensory input or unusual
interests in sensory aspects of the environment
Sensory Processing
ldquoIt is obvioushellipthat sensory processing abnormalities in ASD are distributed rather than localized sensory abnormalities in ASD obviously span multiple dimensions of latency adaptation magnitude and behavior abnormalities with both enhanced and impaired behavior associated with aberrant cortical responses Given this diversity in findings the heterogeneity of ASD and broad variability seen over and over again in the ASD groups almost irrespective of the study it is hard to imagine that one single theory could account for all of these observationshellip It is therefore probable that several mechanisms and neuronal abnormalities most likely at multiple levels (from single neurons through to inter-area connections) all contribute to varying degrees to the abnormal sensory processing observed in ASD It is also likely that no single mechanism is unique to one sensory modality which is why we see such a widely distributed range of abnormalities across modalitiesrdquo Kenet T 2011 Sensory functions in ASD In The Neuropsychology of Autism edited by D Fein New York Oxford University Press
DSM 5 change 3 Each person evaluated will also be described in terms
of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Sensory Processing
ldquoIt is obvioushellipthat sensory processing abnormalities in ASD are distributed rather than localized sensory abnormalities in ASD obviously span multiple dimensions of latency adaptation magnitude and behavior abnormalities with both enhanced and impaired behavior associated with aberrant cortical responses Given this diversity in findings the heterogeneity of ASD and broad variability seen over and over again in the ASD groups almost irrespective of the study it is hard to imagine that one single theory could account for all of these observationshellip It is therefore probable that several mechanisms and neuronal abnormalities most likely at multiple levels (from single neurons through to inter-area connections) all contribute to varying degrees to the abnormal sensory processing observed in ASD It is also likely that no single mechanism is unique to one sensory modality which is why we see such a widely distributed range of abnormalities across modalitiesrdquo Kenet T 2011 Sensory functions in ASD In The Neuropsychology of Autism edited by D Fein New York Oxford University Press
DSM 5 change 3 Each person evaluated will also be described in terms
of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
DSM 5 change 3 Each person evaluated will also be described in terms
of any known genetic cause (eg fragile X syndrome Rett syndrome) level of language and intellectual disability and presence of medical conditions such as seizures anxiety depression andor gastrointestinal (GI) problems
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Currently or by history must meet criteria A B C and D
A Persistent deficits in social communication and social interaction
across contexts not accounted for by general developmental delays and
manifest by all 3 of the following
1 Deficits in social-emotional reciprocity
2 Deficits in nonverbal communicative behaviors used for social
interaction
3 Deficits in developing and maintaining relationships
B Restricted repetitive patterns of behavior interests or activities as
manifested by at least two of the following
1 Stereotyped or repetitive speech motor movements or use of objects
2 Excessive adherence to routines ritualized patterns of verbal or
nonverbal behavior or excessive resistance to change
3 Highly restricted fixated interests that are abnormal in intensity or
focus
4 Hyper-or hypo-reactivity to sensory input or unusual interest in sensory
aspects of environment
CSymptoms must be present in early childhood (but may not become
fully manifest until social demands exceed limited capacities)
DSymptoms together limit and impair everyday functioning
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
DSM-5 Change 4 Fourth the work group added a new category called
Social Communication Disorder This will allow for a diagnosis of disability in social communication without the presence of repetitive behavior
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Naturopathic medicine and the autism community
Naturopathic physicians are poised to provide exemplary primary care of children and adults with autism and developmental disorders
Be mindful of person centered language
Advocate and support vs defeat and recover
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Does this child have a problem Tools to identify a struggle need for a referral
Parent Reported- Ages and Stages Questionaire
ASQ- wwwasqoregoncom
Developmental Milestones checklist (Bright Futures)
Practitioner delivered assessment
MCHAT- Modified checklist for autism in toddlers
18 and 24 months wwwM-chatorg
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
MCHAT wwwM-CHATorg
2 Does your child take an interest in other children Yes No
5 Does your child ever pretend for example to talk on the phone or take
care of dolls or pretend other things Y N
7 Does your child ever use hisher index finger to point to indicate interest in something Yes No
9 Does your child ever bring objects over to you (parent) to show you
something Yes No
14 Does your child respond to hisher name when you call Yes No
15 If you point at a toy across the room does your child look at it Yes No
20 Have you ever wondered if your child is deaf Yes No
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
RITVO (RAADS-R)- Scale for adults Diagnostic scale for adults
64 or less indicates that it is highly unlikely that a patient has autism
A score of 77 or higher indicates a high probablility of ASD
Riva Ariella Ritvoet al The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults An International Validation Study Journal of Autism and Developmental Disorders August 2011 Volume 41 Issue 8 pp 1076-1089
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
This patient needs a referral Who should you refer to
Psychologist
Educational Assessment Early Intervention
Behavioral Pediatrician
Neurologist- if you suspect seizure activity order a sleep deprived EEG and refer
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
The Culture of Autism With the rising population of ASDs- it is critical that
we begin
Supporting listening and advocating
Including individuals with ASD into our society
Accepting differences
Moving beyond the imposition of our cultural norms onto the culture of autism
Karlarsquos ASD Blog on Facebook
ASAN- httpautisticadvocacyorg
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Rethinking Autism
Brain-based or Systemic
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Correlation does not imply mechanism- how but not why
wwwautismwhyandhoworg
Genes Inherited and acquired mutations Gene expression
Environment Too much bad not enough good Different levels of environment Physical biological social emotional
Physiology Molecules ndash different molecules different molecular interactions Biochemistry and metabolism ndash some pathways working harder other pathways stuck Organ systems ndash gastrointestinal immune endocrinehormone
Brain Brain modules under- or over-active Brain networks and connections differently mapped or differently active Brain cells and tissue affected by physiological problems like inflammation and oxidative stress Too much or not enough of brain chemicals like neurotransmitters or neuropeptides Electrophysiology
Total load allostatic load cumulative stress Cumulative impact of genetic vulnerabilities environmental stressors lack of environmental
supports all shift the functioning of the system
Global crisis
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Research Advances in 2013
Deeper Understanding of Link between Chemical Pollutants and Autism
Hundreds of Tiny Mutations Linked to Autism
Insights into Immune Changes amp Autism
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Autism and our planet
Autism may be a development reflecting environmental change
Environmental pollutants continue to be implicated neurodevelopmental issues
Beyond physical toxicants- EMF
Disconnect from Nature and GAIA
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
EPA Builds List of Potentially Dangerous Chemicals
As the rates of learning disabilities and neurodevelopmental conditions rise the Environmental Protection Agency has released a roster of the pollutants likely to contribute to these or other neurological disorders
httpwwwepagovaceace3draftdraft_pdfsACE3NeurodevelopmentalDisordersReviewPackage3-02-11pdf
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
List of Implicated Toxicants 2-ethoxyethyl Acetate ndash a solvent used as a coating for wood metal and other materials sometimes found in
cosmetics Acibenzolar-S methyl -- a fungicide Acrylamide ndash a chemical that is produced naturally in certain foods when they are cooked at high temperatures It is
also manufactured industrially for use in the production of polyacrylamide gels which are used for various purposes including the treatment of drinking water and wastewater and found in cigarette smoke
Aldicarb ndash a pesticide Allethrin ndash a pesticide Aluminum (lactate) -- used in lotions to treat very dry skin Aminopterin ndash chemical originally developed for use in cancer treatment Arsenic -- a semi-metal element which enters drinking water supplies from natural deposits in the Earth or from
agricultural and industrial practices Aspartame ndash an artificial sweetener Benomyl ndash a fungicide Benzene ndash a volatile organic chemical formed through natural processes such as volcanoes and forest fires It is also
formed from industrial processes and is used to make plastics rubber resins and synthetic fabrics like nylon and polyester Benzene is also a natural part of crude oil gasoline and cigarette smoke
Bioallethrin (s-bioallethrin) ndash a pesticide Bis(tri-n-butyltin)oxide ndash a biocide Bisphenol A ndash This chemical is the main ingredient in polycarbonate plastic used to make water bottles baby bottles
and food storage and heating trays and epoxy resin which is used in the lining of most food and beverage cans Butylated Hydroxy Anisole ndash a food additive better known as BHA
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Butylated hydroxytoluene ndash a toluene-based ingredient used as a preservative in food and personal care products
Cadmium ndash a natural element in the Earths crust It is found in food and people can be exposed from smoking cigarettes or breathing cigarette smoke or from water or industrial facilities which release it into the air
Carbaryl -- insecticide
Carbon monoxide -- an odorless and colorless toxic gas
Chlordecone ndash an insecticide
Chlorine dioxide ndash a chemical mostly used to disinfect water
Chlorpyrifos -- insecticide
Cypermethrin --insecticide
DEET ndash a common ingredient in insect repellents
Deltamethrin -- insecticide
Diazinon ndash a pesticide
Dieldrin ndash an insecticide no longer produced in the US but still found in the environment
Ethanol ndash grain alcohol produced from crops such as corn used as a fuel additive solvent and for other purposes
Ethylene thiourea ndash an industrial chemical mostly used to make rubber products but also in the manufacture of fungicides and rodenticides
Fluazinam ndash a fungicide
Heptachlor ndash a non-agricultural insecticide whose use is now very limited
Hexachlorobenzene ndash can be formed as a byproduct during the manufacture of chemicals used as solvents other chlorine-containing compounds and pesticides Small amounts of hexachlorobenzene can also be produced during combustion processes such as burning of city wastes Currently the substance is not used commercially in the United States
Hexachlorophene ndash a disinfectant
Lead ndash This heavy metal occurs naturally in the Earths crust It was formerly used as a gasoline additive and was also commonly added to paint Lead pipes may also contaminate drinking water Currently coal-fired power plants and other industrial uses release lead particles into the air
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Lindane ndash a chemical used to treat scabies and lice Maneb ndash a fungicide Methanol ndash also known as wood alcohol an alternative fuel and other uses Methylparathion ndash a pesticide Monosodium Glutamate ndash a flavor enhancer used as a food additive Nicotine ndash the addictive drug in tobacco Methoxyethanol 2 ndash an organic compound used mainly as a solvent Methylmercury ndash- a form of mercury found in contaminated fresh water and salt water fish It gets into the air
when coal oil or wood are burned as fuel or when mercury-contaminated wastes are incinerated Ozone ndash a gas that occurs both in the Earths upper atmosphere and at ground level Paraquat ndash an herbicide Parathion (ethyl) ndash an insecticide PBDEs ndash Polybrominated diphenyl ethers called PBDEs are used as flame retardants among other purposes
Some types of PBDEs have been banned or phased out but industry has developed others to replace them PCBs (generic) ndash Polychlorinated biphenyls (PCBs) are a group of chemicals that were used as insulation in
electrical transformers and for other industrial purposes They are no longer manufactured but have persisted in the environment
Permethrin ndash an insecticide Phthalate di-(2-ethylhexyl) ndash This phthalate commonly referred to as DEHP is found in many plastic
products Tebuconazole ndash a fungicide Toluene ndash a common solvent found in many consumer goods including floor polish moisturizing cream
lubricating oils paint thinners Tributyltin chloride ndash Manmade organic substances containing the metal tin They are used as pesticides and
biocides in marine antifouling paints and in wood preservatives Trichlorfon ndash an insecticide Trichloroethylene ndash used as a solvent to clean metal parts and for other industrial processes often found as a
water contaminant
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
In Utero Exposures and Autism The only in prenatal exposure well documented in autism is Valproic
acid Bromley RL Mawer G Baker GA Autism spectrum disorders following in utero exposure to
antiepileptic drugs Neurodevelopment GroupNeurology 2008 Dec 2 71(23)1923-4
All contaminants are not equal
Organohalogens higher in mom than baby PCBs higher in baby than mom Mercury is high uniform in all matrices
Larry L Needhamdagger Philippe GrandjeanDaggersect Birger Heinzow Poul J Joslashrgensenpara Flemming NielsenDagger
Donald G Patterson Jrdagger Andreas Sjdindagger Wayman E Turnerdagger and Pal Weihe Partition of Environmental Chemicals between Maternal and Fetal Blood and Tissues Environ Sci Technol Article ASAP Publication Date (Web) December 17 2010
National Childrenrsquos Study wwwnationalchildrensstudygov
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
PDBEs Halt Flames and Neurodevelopment
Cord Blood PDBE levels have neurodevelopmental consequences
bull Samples taken from 329 mothers and children in Manhattan who delivered in proximity to the 9112001 attack
Julie B Herbstman Andreas Sjoumldin Matthew Kurzon Sally A Lederman Richard S Jones Virginia Rauh Larry L Needham Deliang Tang Megan Niedzwiecki Richard Y Wang and Frederica Perera Prenatal Exposure to PBDEs and Neurodevelopment Environmental Health Perspectives 2010118(5)712-719
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Indoor environment counts Increased risk of developing an ASD if living
in a house with PVC flooring Larsson M B Weiss S Janson J Sundell and CG Bornehag 2009 Associations
between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age Neurotoxicology 30 (5)822-31
Increased risk of ASD if living near a freeway Kalkbrenner AE Daniels JL Chen JC Poole C Emch M Morrissey J Perinatal
exposure to hazardous air pollutants and autism spectrum disorders at age 8 Epidemiology 2010 Sep21(5)631-41
Becerra TA Wilhelm M Olsen J Cockburn M Ritz B Ambient Air Pollution and Autism in Los Angeles County California Environ Health Perspect 2013 Mar121(3)380-6 doi 101289ehp1205827 Epub 2012 Dec 17
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Autism and Heavy Metals Children with ASD have high amounts metals Adams JB M Baral E Geis J Mitchell J Ingram A Hensley I Zappia S
Newmark E Gehn RA Rubin K Mitchell J Bradstreet and JM El-Dahr 2009 The severity of autism is associated with toxic metal body burden and red blood cell glutathioine levels Journal of Toxicology doi1011552009532640
Children with ASD have Normal amounts of metals
Albizzati A Moregrave L Di Candia D Saccani M Lenti CNormal concentrations of heavy metals in autistic spectrum disorders Minerva Pediatr 2012 Feb64(1)27-31
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Why heavy metals in Autism Direct Exposure- lead mercury aluminum or
arsenic can sometimes be implicated Faulty Genetics- Epigenetic differences can lead
to sluggish biotransforamationdetoxification and metabolic storage
Walsh WJ Usman A and Tarpey J Disordered Metal Metabolism In a Large
Autism Population Proceedings of the Amer Psych Assn New Research Abstract NR109 New Orleans May 2001
Rose S Melnyk S et al The frequency of polymorphisms affecting lead and mercury toxicity among children with autism Am J Biochem Biotechnol 2008 4(2) 85-94
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
The ldquoVrdquo Word wwwvaccinesafetyeducomponentshtm CDC 2001 Except for influenza thimerosal is removed from or
reduced in all vaccines routinely recommended for children 6 years of age and under manufactured for the US market
Main Preservative 2-phenoxyethanol Aluminum used as an adjuvant
Bishop N J Morley R Day J P Lucas A (1997) Aluminum
neurotoxicity in preterm infants receiving intravenous-feeding solutions The New England journal of medicine 336(22)1557-61
Aluminum exposure in the first six months of life 4mg from vaccines 10mg from breast milk 40mg from dairy infant formula 125 mg from soy based infant formula wwwvaccinechopedu
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Too much too soon Destefano F Price CS Weintraub ES Increasing
Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of AutismJ Pediatr 2013 Mar 29
256 ASD and 752 controls
summation analysis of the content of Antibody-Stimulating Proteins and Polysaccharides which consisted of a summation of the antigen content of each vaccine received
Exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Disconnect From Gaia
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Environment and Genetics
Environmental toxicants interfere with faulty epigenetics and the end result is oxidative
stress and neuroinflammation
Herbert MR Contributions of the environment and environmentally vulnerable physiology to autism spectrum disordersCurr Opin Neurol 2010 Apr23(2)103-10
Deth R Muratore C Benzecry J Power-Charnitsky VA Waly M How
environmental and genetic factors combine to cause autism A redoxmethylation hypothesis Neurotoxicology 2008 Jan29(1)190-201
Herbert MR Russo JP Yang S et al Autism and environmental genomics
Neurotoxicology 2006 27(5)671-84
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Genetics and ASD
Age of father will contribute to the frequency of de novo genetic mutations
Kong A Frigge ML Masson G et al Rate of de novo mutations and the importance of fathers age to disease risk Nature 2012 488(7412) 471-5
Sanders SJ Murtha MT Gupta AR et al De novo mutations revealed by whole-exome sequencing are strongly associated with autism Nature 2012 485(7397) 237-41
So what mutations are we looking at
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Enzyme SNPrsquos Studied In Autism
MTHFR - Methylenetetrahydrofolate reductase Defective folate metabolism
Elevated homocysteine levels
Defective ability to methylate DNA
Global loss of methyl groups James SJ Melnyk S Jernigan S Hubanks A Rose S amp Gaylor DW (2008) Abnormal
Transmethylationtranssulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism Journal of Autism and Devopmental Disorders Published online only July 11 2008
COMT-Catechol-O-methyltransferase Kenneth D Gadow Jasmin Roohi Carla J DeVincent Sarah KirschEli Hatchwel Association
of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety ADHD
and Tics in Children with Autism Spectrum Disorder J Autism Dev Disord (2009) 391542ndash
1551
OBrien R A Semenuk G Coleman M and Spector S (1976) Catechol-O-
methyltransferase activity in erythrocytes of children with autism Clinical and Experimental
Pharmacology and Physiology 3 9ndash14
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Enzyme SNPrsquos Studied In Autism CBS - Cystathionine Beta- Synthase
Joins the methyl and sulfur pathways
This is a one-way reaction that permanently removes homocysteine from the methionine cycle and initiates the transsulfuration pathway for the synthesis of cysteine and glutathione
No research ndash only presumptive at this point
Glutathione-S-transferase
Conjugate glutathione with toxins for Phase 2 biotransformation and elimination
Williams TA Mars AE Buyske SG Stenroos ES Wang R Factura-Santiago MF Lambert GH Johnson WG Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype Archives of Pediatrics amp Adolescent Medicine 161(4)356-61 2007 Apr
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
What should we do about it Education and Awareness
Limit Exposure
Everyday detox
Dietary intervention
Methylation support GSH
Investigate toxic levels more thoroughly
Treat more aggressively when toxicants are suspected and confirmed
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Autism ldquoPhenomerdquo Project Medical evaluations An initial exam is conducted by a pediatrician with expertise in
developmental disorders Standard data on height weight and head circumference is gathered as well as blood samples Some of these samples are gathered from siblings and parents as well Parents are asked questions related to the childs exposures to environmental toxins household products and about their dietary habits
Environmental exposuresepidemiology Several lines of evidence suggest that more than just genes determine whether or not a child will have autism The drug thalidomide viruses and mercury are among the non-genetic causes that have been implicated as causes of the disorders Therefore blood of children and mothers are being examined for the presence of metals and environmental toxins
Behavior and neuropsychology These assessments consist of established diagnostic interviews tests parental questionnaires and observational schedules
Genomics This part of the study utilizes the latest in genetic profiling the microarray to assess which genes are turned on - and at what levels - in children with autism compared to children without the disorder
Brain structure MRI EEG data
Immune function -determining the kind and number of antibodies found in the blood serum of patients and look for markers of inflammation hormones and viruses
UC Davis MIND Institute- 1800 kids- WOW
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
wwwBioInitiativeorg Findings in Autism (ASD) Consistent with
Electromagnetic Fields (EMF) and Radiofrequency Radiation (RFR)
Martha Herbert MD PhD
Pediatric Neurology TRANSCEND Research Program Massachusetts General Hospital
Harvard Medical School Cindy Sage MA
For the BioInitiatve Working Group December 2012
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
EMF and RFR in Autism Electromagnetic Frequency and Radio Frequency Radiation
Exposures have outpaced precautions
ldquoThe deployment of new technologies is running ahead of any reasonable estimation of possible health impacts and estimates of probabilities let alone a solid assessment of risk However what has been missing with regard to EMF has been an acknowledgement of the risk that is demonstrated by the scientific studies There is clear evidence of risk although the magnitude of the risk is uncertain and the magnitude of doing nothing on the health effects cost to society is similarly uncertain This situation is very similar to our history of dealing with the hazards of smoking decades ago where the power of the industry to influence governments and even conflicts of interest within the public health community delayed action for more than a generation with consequent loss of life and enormous extra health care costs to societyrdquo
- Sage C and D O Carpenter 2009 Public health implications of wireless technologies
Pathophysiology 16 (2-3)233-46
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
EMF and RFR in Autism Neuropathology of ASD demonstrates striking parallels
in the physiological impacts of electromagnetic frequency and radiofrequency exposures (EMFRFR)
molecular cellular and tissue damage
cellular stress (oxidative stress the heat shock response and protein misfolding)
injury of membranes
aberrant calcium signaling
compromise of junctions and barriers
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
What to do about it Children with existing neurological problems that include cognitive learning
attention memory or behavioral problems should as much as possible be
provided with wired (not wireless) learning living and sleeping environments
Special education classrooms should aim for no wireless conditions to reduce
avoidable stressors that may impede social academic and behavioral progress
All children should reasonably be protected from the physiological stressor of
significantly elevated EMFRFR (wireless in classrooms or home environments)
School districts that are now considering all-wireless learning environments
should be strongly cautioned that wired environments are likely to provide better
learning and teaching environments and prevent possible adverse health
consequences for both students and faculty in the long-term
Monitoring of the impacts of wireless technology in learning and care
environments should be performed with sophisticated measurement and data
analysis techniques that are cognizant of the non-linear impacts of EMFRFR and
of data techniques most appropriate for discerning these impacts
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Immune Abnormalities Hsiao EY McBride SW Chow J Mazmanian SK Patterson PH Modeling an autism
risk factor in mice leads to permanent immune dysregulation Proceedings of the National Academy of Sciences 2012 109(30)
Atladoacutettir HOacute Henriksen TB Schendel DE Parner ET Autism after infection febrile episodes and antibiotic use during pregnancy an exploratory study Pediatrics 2012 Dec130(6)e1447-54 doi 101542peds2012-1107 Epub 2012 Nov 12 little evidence that various types of mild common infectious diseases or febrile episodes during
pregnancy were associated with ASDinfantile autism
maternal influenza infection was associated with a twofold increased risk of infantile autism
prolonged episodes of fever caused a threefold increased risk of infantile autism
and use of various antibiotics during pregnancy were potential risk factors for ASDinfantile autism
ldquoFuture doctors will need to correct the postmodern tendency toward immune dysregulation Evolution has provided us with a road map the original accretion pattern of the superorganism Preventive medicine will need by strange necessity to emulate the patterns from deep in our pastrdquo Moises Velasquez-Manoff
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Emerging treatments for ASD
Beyond therapy (speech behavioral QiGong and Occupational) early intervention diet nutrition homeopathy detox supporthellip now what
Novel Nutraceutical and Pharmaceutical treatments are validating themes that are important to naturopathic medicine
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Folate Autoantibodies in ASD Frye RE Sequeira JM Quadros EV James SJ Rossignol DA Mol
Psychiatry Cerebral folate receptor autoantibodies in autism spectrum disorder 2013 Mar18(3)369-81 doi 101038mp2011175 Epub 2012 Jan 10
Testing contact Department of Biochemistry BSB 7-15
SUNY Downstate Med Center
450 Clarkson Avenue
Brooklyn NY 11203 USA
Ph 718 270-4203
Fax 718 270-3316
E Mail Edwardquadrosdownstateedu
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
When to suspect CFD Low-functioning autism Mitochondrial disease or dysfunction Rett syndrome Epilepsy or seizures Abnormal electroencephalogram subclinical electrical discharges or slowing Ataxia Microcephaly Dyskinesia choreoathetosis ballismus Irritability Insomnia Frontotemporal atrophy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Folate Supplementation Start folinic acid at dose of 05 mgkgday in two divided
doses and increase to 1-4 mgkgday in two divided doses (max 50 mgday) I have been using 5-MTHF in doses of 1-5 mg but moving to Calcium Leucovorin when needing to go above those doses
Discontinue drugs that can interfere with folate metabolism
Consider cobalamin supplementation (vitamin B12) Stop folic acid supplementation Start a cowrsquos milk-free diet Monitor for changes in cognition and behavior Monitor adverse effects
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Arbaclofen Seasides drug STX209 or arbaclofen works to control an
overabundance of signaling or noise at brain synapses by reducing the amount of the neurotransmitter glutamate that is available in the brain
First studied with Fragile X
Arbaclofen = GABA agonist
GABA 250-3000 mg day
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Oxytocin Kumsta R Hummel E Chen FS Heinrichs M Epigenetic regulation of
the oxytocin receptor gene implications for behavioral neuroscience Front Neurosci 2013 May 23783
Anagnostou E Soorya L Chaplin W Bartz J Halpern D Wasserman S Wang AT Pepa L Tanel N Kushki A Hollander E Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders a randomized controlled trial Mol Autism 2012 Dec 53(1)16 doi 1011862040-2392-3-16
Found differences after six weeks of treatment- quality of life and social cognition
Stavropoulos K K M and Carver L J (2013) Research Review Social motivation and oxytocin in autism ndash implications for joint attention development and intervention Journal of Child Psychology and Psychiatry 54 603ndash618
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Oxytocin Available as a daily nasal spray or sublingual drop
No taste no smell no burn
Dose is 10 to 40 units per day
Compounded
No documented or observed negative side effects
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Decreased Tryptophan metabolism Boccuto L Chen CF Pittman AR Skinner CD
McCartney HJ Jones K Bochner BR Stevenson RE Schwartz CE Decreased tryptophan metabolism in patients with autism spectrum disorders Mol Autism 2013 Jun 34(1)16
Decreased tryptophan metabolism may alter brain development neuroimmune activity and mitochondrial function
Decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Melatonin Malow B Adkins KW McGrew SG et al Melatonin for
sleep in children with autism a controlled trial examining dose tolerability and outcomes J Autism Dev Disord 2012 Aug42(8)1729-37
Dose of 1-3 mg qhs significantly improved sleep in children with ASDs
No negative side effects were observed
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
NAC- now in phase 2 trial Hardan AY Fung LK Libove RA Obukhanych TV Nair S Herzenberg
LA Frazier TW Tirouvanziam R A randomized controlled pilot trial of oral N-acetylcysteine in children with autism Biol Psychiatry 2012 Jun 171(11)956-61
N-Acetyl Cysteine
Improvements in irritability hyperactivity and stereotypy
Dose 900 mg TID
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Qi Gong Massage
Qigong Sensory Training (QST)
wwwqstiorg
Parent delivered
May see improvements in sensory symptoms sleep and bowels
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
Remember the foundation Clean up the diet and ADD Nutrition
Heal the gut mind the brain ensure sleep
Address allergies immune issues and sensitivities
Methyl B12 injections q 3d (or other methylation support)
Get outside Commune with animals and nature
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy
QUESTIONS
Mind in the Eyes Test httpwwwquestionwritertrackercomquiz61Z4MK
3TKBhtml
It is not as easy as you think Do you think this is an accurate reflection of social competancy