Autism Spectrum Disorders

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Autism Spectrum Disorders

Basic Characteristics

• Description

Autism Spectrum Disorders is a clinical description of the developmental disorders which are characterized by impaired language development, social development, and learning.

They include:

1. Autism
2. PPD-NOS
3. Asperger's Syndrome
4. Rett Syndrome
5. Childhood Disintegrative Disorder

Children with ASD have extremely delayed development. Symptoms of this disorder usually start to appear between 12 to 36 months and consist of not reaching normal development benchmarks such as babbling by 12 months, speaking by 16 months, or a gradual loss of language or social skills. All children with ASD show deficits in social interactions, verbal and nonverbal communication. They may also show repetitive behaviors and interests, or aggressive behavior.

Although all children with ASD show similar deficits, the depth of these deficits can range drastically. Some have very mild deficits like in Asperger's Syndrome, where children have high levels of vocabulary and language skills. Others may have little to no spoken language functionality.

• Causes

Scientists have not found the exact cause of ASD, although all would agree that there is a genetic basis. Strong genetic factors have been found for some of these disorders such as in Rett Syndrome, and there are simple tests for diagnostic purposes for these disorders.

The difficulty in finding the cause of ASD partially lies in its definition, and partially on the complex interplay between genes that happens during development. ASD, like most other behavioral disorders, is diagnosed based off of observable characteristics of the child. However, these diagnosis offer no direction as to which specific genes are defective. Furthermore, two patients with ASD can present very similar symptoms and yet have different defective genes or causes. For example, Rett Syndrome is caused by mutations in the gene MeCP2 while Tuberous Sclerosis is caused by mutations in TSC1 and TSC2. It should be noted that both Rett Syndrome and Tuberous Sclerosis are very rare.

• History

Prior to the 1970's, many people thought Autism Spectrum Disorders were a result of psychological causes, such as having an aloof mothering style. However, during the 1980's people began to note that chromosomal disorders and rare syndromes often co-occurred with ASD. As a result, people began to suspect that ASD could have genetic underpinnings. These suspicions were confirmed when, after the development of the ADI-R and ADOS as diagnostic tools and other technical advances, the first candidate gene association and resequencing studies, followed by whole-genome linking studies were done in the late 1990's. These studies were used to identify loci of potential interest.

Core Deficits

Those who have ASD have identifiable core deficits recognized by scientists and clinicians.

1. Core Deficit of Joint Attention
2. Core Deficit of Social Communication
3. Repetitive behaviors or interests

Treatments

There are no drugs that can “cure” ASD. There are a variety of treatments available which aim to improve social and communication skills. Because of the complexity of ASD, there is no one treatment that works equally well for all people with ASD. Some common treatments are:

• Applied Behavior Analysis interventions
• Joint Attention interventions

Some clinicians may prescribe medications to target certain symptoms.

Neuroimaging

It has been hypothesized in the Mirror Neuron System Theory of Autism that the mirror neuron system plays an integral role in mediating understanding of emotional states of others, and thus the social/communication deficits in ASD arise because of differences in activation of the Mirror Neuron System (MNS). However, since many different areas of the brain can participate in complex social/communicative tasks, it is difficult to single out just one neural area responsible for the widespread abnormalities in socialization and communication experienced by patients with ASD. Much of current neuroimaging research in ASD operates under one of two different camps that attribute autism to different areas of less activation in the brain.

1. Theory of Mind-Patients with ASD show lower or no activation in midline structures as compared to a control groups in many tasks, lending credence to the 'Theory Of Mind' explanation for social/communication deficits in patients with ASD. In this theory, patients with ASD have lower activation of mirror neurons in the midline structures which are responsible for "reflecting" about others' emotions or wants^[1],. Thus, patients have social/communication deficits because they have are unable to process the meaning of other peoples' emotions, which suggests a problem in executive processing.
2. Simulation of System- Scientists who believe that the Simulation of System theory explains the social/communication deficits in ASD patients focus their research on shared circuits that are involved in both one's own emotions and other's emotions. Numerous studies have shown that when subjects witness a goal oriented task many different types of neurons are activated in addition to those in the midline structures. For example, when a person watches another person drink a glass of milk with an expression of disgust on his face, the premotor and parietal areas are activated for the action itself, the insula areas are activated in response to the emotion of disgust, and the secondary somatosensory area is activated for the sensations involved in the task. These are the same areas that would have been activated if we drank the milk and were ourselves disgusted. Thus, we are able to understand others' emotional states and intentions because contextual cues activate the same neural circuits that are activated when we perform the same task. However, patients with ASD show diminished activation of these areas as compared to control groups. So, in this theory, the social and communication difficulties arise in patients with ASD because these areas are less activated. Consequently, they have difficulty "understanding" another's actions.¹

These two theories are not entirely incompatible and there have been some hypothesis on how the two theories could be integrated to provide a better explanation for the differences seen.

Facial Processing Patients with ASD show less interest in human faces. Normal people perform much better at tasks where they have to identify or match faces that are upright versus inverted. ASD children on the other hand, show a noticeably less pronounced 'inversion effect' as compared to the normal population. Some scientists speculate that this may be because children with ASD process faces similarly to regular objects rather than assigning particular significance to faces, thereby reducing the inversion effect. Another hypothesis is that ASD children may engage more in component processing rather than configural processing, thereby making the activation difference between processing upright faces versus inverted faces smaller. Differences in activation areas are in the frontal cortex and the amygdala, perhaps reflecting a difference in processing the meaning and significance of faces. <ref>Bookheimer.</ref>

Genetics

A host of genes of interest have been identified through gene association studies, resequencing and, recently, the assessment of copy number variation (CNV).In particular, given the pathology of ASD, genes dealing with electrical conductance and neural transmission have been popular sites of study since synaptic dysfunction has been suggested as a unifying theme behind the various disorders in ASD.

Most approaches to finding loci of interest are under one of two hypotheses:

1. ASD is a result of interplay between many genes
2. There is one principle gene which contributes to many aspects of the disease.

The idea that the symptoms of ASD is a result of the interaction of many different genes has been supported by linkage studies, and the fact that although many genes have been identified with causing ASD symptoms, each of these individual genes do not cause more than 1-2% of all ASD cases. However, data mining techniques such as hierarchical clustering and principle components analysis find that it is highly likely that there is 1 continuously distributed factor contributing to many aspects of ASD, thereby validating the existence of the second hypothesis. Additionally, statistical analysis of ASD family data suggest a large portion of ASDs may be the result of dominant de novo mutations that have reduced penetrance in families.

Some likely candidate genes that have been explored include

Gene	Function	Location
UBE3A	transcribed protein is an enzyme that works in protein degradation	15q11-q13
GABRB3	encodes a member of of a ligand gated ionic channels responsible for inhibition in nervous system	15q11-q12

Successful linkage studies in the past have been mostly based on affected sibling-pair designs in multiplex families. However, there were no genome wide significant results probably because of small effect sizes that were a result of any single gene. Even large scale studies showed only minor overlap, likely because of variety of phenotypes in ASD. Recently though, use of endophenotypes and QTL mapping have increased the power of linkage and association studies.

Related Information

• Task or test associated with this construct (vote for your favorite, or nominate a new one by editing this page):
  • ADOS
  • ADI-R

• Indicators (dependent variables, conditions, or contrasts; measurement variables used for analysis) associated with this construct (vote or nominate by editing this page):

• Closely related pages (vote or nominate related pages by editing this page):

• CNP Level
  • Syndrome

External Resources

• Links out:
  • Google: ADHD
  • Wikipedia: ADHD
  • PubMed: ADHD
  • -ucla cognitive atlas- (coming soon!)

• Database links

Citations

1. Keysers, Christian and Valeria Gazzola. Integrating simulation and theory of mind: from self to social cognition. Trends in Cognitive Sciences. Vol 11:5 pg. 194-6; 2007