What is known about autism: genes, brain, and behavior

Am J Pharmacogenomics. 2005;5(2):71-92. doi: 10.2165/00129785-200505020-00001.

Abstract

Autism is a neurodevelopmental disorder of genetic origins, with a heritability of about 90%. Autistic disorder is classed within the broad domain of pervasive developmental disorders (PDD) that also includes Rett syndrome, childhood disintegrative disorder, Asperger syndrome, and PDD not otherwise specified (PDD-NOS). Prevalence estimates suggest a rate of 0.1-0.2% for autism and 0.6% for the range of PDD disorders. There is considerable phenotypic heterogeneity within this class of disorders as well as continued debate regarding their clinical boundaries. Autism is the prototypical PDD, and is characterized by impairments in three core domains: social interaction, language development, and patterns of behavior (restricted and stereotyped). Clinical pattern and severity of impairment vary along these dimensions, and the level of cognitive functioning of individuals with autism spans the entire range, from profound mental retardation to superior intellect. There is no single biological or clinical marker for autism, nor is it expected that a single gene is responsible for its expression; as many as 15+ genes may be involved. However, environmental influences are also important, as concordance in monozygotic twins is less than 100% and the phenotypic expression of the disorder varies widely, even within monozygotic twins. Multiple susceptibility factors are being explored using varied methodologies, including genome-wide linkage studies, and family- and case-control candidate gene association studies. This paper reviews what is currently known about the genetic and environmental risk factors, neuropathology, and psychopharmacology of autism. Discussion of genetic factors focuses on the findings from linkage and association studies, the results of which have implicated the involvement of nearly every chromosome in the human genome. However, the most consistently replicated linkage findings have been on chromosome 7q, 2q, and 15q. The positive associations from candidate gene studies are largely unreplicated, with the possible exceptions of the GABRB3 and serotonin transporter genes. No single region of the brain or pathophysiological mechanism has yet been identified as being associated with autism. Postmortem findings, animal models, and neuroimaging studies have focused on the cerebellum, frontal cortex, hippocampus, and especially the amygdala. The cerebello-thalamo-cortical circuit may also be influential in autism. There is evidence that overall brain size is increased in some individuals with autism. Presently there are no drugs that produce major improvements in the core social or pragmatic language deficits in autism, although several have limited effects on associated behavioral features. The application of new techniques in autism research is being proposed, including the investigation of abnormal regulation of gene expression, proteomics, and the use of MRI and postmortem analysis of the brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autistic Disorder / genetics*
  • Autistic Disorder / pathology
  • Autistic Disorder / physiopathology
  • Brain / pathology
  • Brain / physiopathology*
  • Genetics, Behavioral / methods*
  • Genetics, Behavioral / trends
  • Humans
  • Proteomics / methods
  • Proteomics / trends