Neuropsychology of Autism Spectrum Disorder ANDREA CAVALIERE

Our Discussion 1. DSM-V

2. History/Discovery

3. Epidemiology

4. Aetiology

5. Neuroanatomy

6. Neurodevelopment

7. Neuroendocrinology

8. Neurotransmission

9. Genetics

10. Clinical assessment and testing

DSM-V Diagnoses1. Persistent deficits in social communication and interaction:

- Deficits in social-emotional reciprocity, nonverbal communicative behaviours and developing/maintaining relationships.

2. Restricted and repetitive behavioural patterns or interests, featuring 2 of the following traits:

- Repetitive speech, movements or use of objects.

- Excessive devotion to routines or extreme resistance to change

- Highly fixated and/or abnormal interests.

- Hyper- or hypo-reactive responses to sensory input or unusual interest in visual environmental cues.

3. Onset during early childhood.

4. Significant impairment.

In plain English…

Autistic [social] aloneness (difficulty to interact with others)

Issues in verbal and non-verbal communication

Odd and repetitive behaviours

https://www.youtube.com/watch?v=SiQtKWkIt5o

What is meant by “Spectrum”?

Signs and symptoms fall within a continuum ranging from severe to less severe impairments.

This continuum encompassed: Autism, Asperger syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS)

However the recent DSM-V now classifies the spectrum simply from high-functioning autism to severe autism.

Or Severe Autism

History of Autism Spectrum Disorder (ASD)

ASD was first observed by psychiatrist Leo Kanner in 1943 when he was studying a group of infants; hence he coined the term “early infantile autism” in his paper published in 1943.

Kanner witnessed children who were “socially aloof”, were mute or had abnormal speech and resistant to change in routine. He noted how alert and intelligent theses children appeared.

History of Autism Spectrum Disorder (ASD)

However, Hans Asperger published his work in 1944 on older children and noted the abnormalities in their socialization skills, their motor skills, their body language and were self absorbed in unique interests. However he describes that these children were “borderline, normal or superior” in intelligence but still suffered learning impairments.

Both Kanner and Asperger vividly described their subjects, making their works the most popular in the 1940s, though both of their works overlapped.

Epidemiology In the US, while monitoring children aged 8 years at several sites,

shows that the prevalence of ASD increased from 67 per 10 000 children to 114 per 10 000 (2008).

The increase may be due to heightened awareness of ASD and changes in diagnostic standards (i.e. DSM-IV definition on ASD was general)

Caucasian children have the highest rate of ASD while Hispanic children have the lowest rate.

Prevalence is greater in males than females (~5:1)

Aetiology Using twin studies with homozygous twins, many researchers now believe the main cause of autism is genetic.

There seems to be a plethora of genes that may cause ASD but the development of ASD may result from genetic factors, as well as the pre/postnatal environment.

Environmental effects on the prenatal fetus include exposure to: valproic acid, thalidomide, alcohol, cocaine, toxic metals, air chemicals.

Maternal and fetal inflammation caused by viral/bacterial infections, diabetes and so on can also the root of ASD development.

By Dr. Dorota A. Crawford via http://www.yorku.ca/dakc/RESEARCH.html

Neuroanatomy In autistic adolescent brains, generally speaking, certain major neural regions are always affected in almost every case. The regions impacted give rise to a cluster of symptoms described earlier:

Neurodevelopment

During fetal development, corticogenesis occurs (formation of the cortex). The marginal zone and subplate of the fetal brain, as researchers believe, highly express genes linked to ASD, like Reelin (glycoprotein that aids in neural migration) and TBR1 (aids in neural differentiation and axon guidance).

Compared to controls, autistic brains (developing and young) show an increase in gray matter and even greater increase in white matter. Thus, their brains have a larger than usual brain volume compared to controls. The enlargement in gray and white matter occur in the temporal, parietal, and especially the frontal lobe. One study found that the genu and the splenuim of the corpus callosum in autistic brains have a 14% reduction in volume. Although other studies found opposite results.

In post-mortem studies, there have been consistency over the decreased cell sizes within the hippocampus and amygdala. These cell are also closely dense to one another.

The Purkinje cells in the cerebellum were found to be reduced in number.

Cell bodies in layer III in the neocortex are more numerous and dense than the controls.

There is also a lack of synaptic pruning during development in autistic brains.

Microglial samples show an activated morphology and they secrete a cytokine profile that display a pro-inflammatory state. A post-mortem study found that autistic brains had a decreased number of long-distance axons (white matter) and had increased branching with thinner myelin.

Neuroendocrinology Abnormal levels of testosterone in autistic children have been studied and it may be the cause of violent behaviour; both explosive and non-explosive aggression. Cortisol has been observed to also contribute to ASD; it is associated with increases in repetitive behaviours. Oxytocin is also associated with repetitive behaviour; oxytocin levels are negatively related to compulsive and restricted behaviour.

Neurotransmission A deficiency in GABA.

There are reported reduced GABAA receptors within the hippocampus ,cingulate gyrus, frontal lobe and amygdala in autistic brains, leading to inhibitory discrepancies in speech and social skills.

Researchers consistently find hyperserotonemia (high levels of serotonin) within ASD individuals. Serotonin’s main transporter, 5-HT, is disrupted.

Increased serotonin affects emotion centres such as the amygdalae, region associated with social memory and bonding.

There is also growing evidence that excitotoxicity occurs in autistic brains (due to an excess glutamate).

Genetics Males are about four times more likely than females to develop ASD.

Using twin studies, monozygotic twins (concordance rate of 70%) with a genetic disposition for autism are highly likely to develop ASD than dizygotic twins.

Serotonin transporter (5-HT) gene, SLC6A4, is seen to be disrupted with autistic brains.

Other numerous studies discuss various genes on multiple chromosomes responsible for ASD. A few will be discussed:

Clinical Assessment The Modified Checklist for Autism in Toddlers (M-CHAT), is a psychological evaluation to assesses risk for ASD for children between 16-30 months (displays good reliability and validity)

It contains 20 questions for the child’s parent(s).

Scores that are within medium or high risk ranges may not guarantee a diagnosis; it depends on a doctor’s interpretation.

Cons of this assessments include biases in self-reports, factors like sociocultural/economic background can impact results and doctors may not detect certain behaviours symptomatic to ASD.

Clinical Tests Those with ASD score lower than controls on the Cambridge mindreading face-voice battery for children (CAM-C), which tests recognition of complex emotional expressions (both facial and vocal).

In longitudinal studies, ASD participants had low scores on executive functions task such as the Tower of Hanoi/London test and the Wisconsin Card Sort Test (WCST) and did not show much improvement after 3 years.

In Theory of Mind tasks, ASD individuals score lower than controls.

However, they score just as well as control in central coherence tacks; to understand the general context or the big picture.

Treatment Various drugs such as stimulants, antidepressants and antipsychotics have been prescribed for those with ASD.

ABA (Applied Behaviour Analysis) is the most widely used treatment of ASD with a large database of empirical evidence to support its practise.

It involves intensive one-on-one or small group cognitive-behavioural training. Essentially a teacher or caregiver can condition these children to communicate better and apply newly developed skills in a social or academic setting.

IBI (intensive behavioural intervention) is quite similar to ABA, but it is done by a trained behavioural analyst, it includes intensive behaviour therapies designed to fit each client and IBI prepares ASD children for school (usually entering kindergarten).

Animal Models Mice and rat models are used for neuroanatomical studies and in neurogenetic studies (knock out). Other species of animals include zebra fish, guinea pigs; they are used for genetic and neurobiological studies.

ConclusionMyths (i.e. vaccines, contributions to society, “retardation”) What impacts more? Genes or environment? Treat or accept? (My yoga teacher)

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