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2010 PowerPoint presentation Dr. Rajakumar CME Boston IMHO Convention
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Brain Abnormalities in Autism
N. Rajakumar, M.B.B.S., Ph.D.
University of Western Ontario
London, ON, Canada
nrajakum@uwo.ca
Autism Vs Autism Spectrum Disorders
Pervasive Developmental
Disorders
! Autism
! PDD not otherwise specified
! Asperger syndrome
! Rett syndrome
! Childhood disintegrative
disorder (“acquired autism”)
ASD
DSM IV; ICD-10
Autism - Clinical Features
Core Features:
! Impaired social interaction
! Impaired communication (verbal & non-verbal)
! Repetitive, stereotyped & restricted behavior
Certain abnormalities may be noticeable as
early as 6 months, but diagnosis is usually
made by 2.5-3 yrs
Co-morbidities:
! Intellectual disability 40-80% of patients
! Hyperactivity 60%
! Hypotonia 50%
! Anxiety 40-80%
! OCD 40%
! Aggressiveness 8-32%
! Self-injurious 35%
! Sensory abnormality 80-90%
! Seizure 5-50%
! GI symptoms 30-90%
! Sleep problem 50-70%
Lancet (2009) 374:1627-38
! Effective therapies are available for most
co-mobidity and therefore, identification and
treatment of co-morbidities are important and
will improve the quality of life
ASD - Treatment
! Outcome is better with
" early detection (?)
" intensive behavioral therapy
" special education
! No pharmacological therapy available for
core symptoms
e.g., Discrete trial training - effective in >50% of pts.
! Do not know which treatment is effective
and for whom
ASD - Prognosis
! No cure
! No remission
! Some symptoms get better with or without
treatment
! Develop coping strategies as adults
! Many need a continued support
Why study autism?
! A common psychiatric problem in children
" Prevalence 1-2 per 1000 for autism
(6/1000 for ASD)
US Prevalence
" Is it increasing?
# Changes in diagnostic practice
# Increased public awareness
# A “true increase”?
Autism - Cause
! Genetic predisposition
! Early developmental insults
! Environmental factors
? Virus/drugs/toxins at <8 weeks of gestation
? Environmental toxins (metals - Hg)
? Abnormal gut flora (endotoxins)
? Immunological/autoimmune (viral, vaccine)
Autism - Genetics
! Highly heritable traits: >0.7 for autism
>0.9 for ASD
! >60% monozygotic twins are concordant
(ASD)
! 20-50 times increased chances for the next
child to develop autism
!10-20% of ASD cases have identifiable genetic
changes
! >40 genetic abnormalities have been described
! Many are involved in synaptic development
A synapse
Those in RED are proteins of ASD candidate genes
Excess number of synapses are formed during
development and most are then eliminated
Schizophrenia diagnosis
Abnormal development of synapses may
contribute to autism
(2009) 19:231-4
What do we find in autistic patients?
! Most consistent finding is increased head
circumference
! Brain size is normal at birth, but in 20% cases
it increases and then regresses to normal size
Autism (1298 ± 88 ml)
Normal (1179 ± 71 ml)
0.9
1
1.1
1.2
1.3
1.4
Series1
Series2
Birth 6 yrs
Brain size Annual Review of Medicine (2009) 60:367-80
Neuroradiology (2010) 52:3-14
Postmortem findings
• Are inconsistent
! Increased cell packing and decreased cell
size in amygdala and hippocampus
! Decreased # of Purkinje cells in the
cerebellum
! Poor grey-white boundary
! These findings suggest some form of
Neurodevelopmental defecte.g., abnormal neurogenesis/migration
Autism Control
Volume is increased in cerebral (18%)
and cerebellar (39%) white matter, and
cerebral cortical gray matter (12%)
compared to normal children
Recent MRI studies, however, strongly
indicate that the volume increase is mainly in
the white matter in autism patients
Neurology (2001) 57:245-54
Our studies also show increased white
matter volume in autistic children
Human Brain Mapping (2009) 30:3887-900
One of our study in shows decreased size of
corpus callosum (mainly in the anterior third)
Biol. Psychiatry (2006) 60:218-25
f-MRI findings:
! Differences in patterns of activation of
brain areas and timing of synchronization
! Decreased and abnormal activation of
fusiform cortex (face area)
Control Autism
! Decreased activation of mirror neurons
Control Autism
! f-MRI studies indicate that autistic
children show Decreased functional
connectivity
i.e., abnormal connections among
functionally related brain areas
An MRI technique capable of imaging white
matter tracts, Diffusion Tensor Imaging, is
rapidly improving
We and others are beginning to employ this in autism
BRAIN TRAINING: New Hope for Children with
Developmental Delaysby Dr. Michelle Lewis MacAlpine
Scientists have learned more about how brains repair themselves in the past ten years
than they did in the previous ten thousand. New information about how the brain is
affected by sensory experiences, hormones, immune molecules and digestive
processes is helping revolutionize treatments for developmental disorders that were
once believed to be irreversible. This book guides the reader through the science and
the methods behind these new ideas and describes how to stimulate play, language,
and social development even in severely delayed children. Written in clear language
with plenty of practical advice, this book is an important resource for parents and
professionals alike. VIEW TABLE OF CONTENTS View Chapter
All kinds of “attractive things” out there …..be cautious!
e.g.,
Published online 20 April 2010 | Nature 464, 1111 (2010) | doi:10.1038/4641111a
No gain from brain training: Computerized mental workouts don't boost
mental skills, study claims.
The largest trial to date of 'brain-training' computer
games suggests that people who use the software to
boost their mental skills are likely to be disappointed.
The study, a collaboration between British researchers
and the BBC Lab UK website, recruited viewers of the
BBC science program Bang Goes the Theory to practice
a series of online tasks for a minimum of ten minutes
a day, three times a week, for six weeks. In one group,
the tasks focused on reasoning, planning and problem-
solving abilities — skills correlated with general intelligence. A second
group was trained on mental functions targeted by commercial brain-
training programs — short-term memory, attention, visuospatial abilities and
maths. A third group, the control subjects, simply used the Internet to find
answers to obscure questions. A total of 11,430 volunteers aged from 18 to
60 completed the study, and although they improved on the tasks, the
researchers believe that none of the groups boosted their performance on
tests measuring general cognitive abilities such as memory, reasoning and
learning.
Take home massage…
! Autism is a developmental brain disorder
! Heterogeneous diagnosis - based on meeting
criteria (and many of them are subjective)
! Symptoms are often loosely characterized
(?shared by other disorders, and are
deviation/deficits from normal traits)
! Autistic traits have strong genetic basis -
likely associated with rare interactions of
common mutations
! No pharmacological treatment is available for
core symptoms
! Behavioral therapy and special education
may improve certain core symptoms in
certain cases
! Treating co-morbidity may improve the quality
of life
Take home massage… (cont.)
! May involve abnormal development of
synapses
! May involve abnormal formation &
migration of neurons
! May have abnormalities of white matter
tracts of the brain
! May have “disconnection” among
functionally connected brain areas
Take home massage… (cont.)
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