The Neurobiological Context of Autism

Autistic disorder (AD) is a complex neuropsychiatric disorder of neurodevelopmental origin, where multiple genetic and environmental factors may interact, resulting in a clinical continuum. The genetic component is best described by a multilocus model that takes into account epistatic interactions between several susceptibility genes. In the past ten years enormous progress has been made in identifying chromosomal regions in linkage with AD, but no single gene has emerged yet as a major factor of genetic liability. Neuroanatomical findings point to early dysgenetic events taking place in the cerebral cortex, cerebellum, and brains stem. At the cellular level, disease mechanisms may include altered cell migration, increased cell proliferation, decreased cell death, or altered synapse elimination. In contrast to other diseases of the nervous system (e.g. Parkinson’s and Alzheimer’s disease) neurochemical findings in AD point to involvement of multiple neurotransmitter systems. The serotoninergic system has been intensively investigated in this respect, but other neurotrasmitter systems known to be involved in cognitive functions (e.g. the cholinergic system) are coming under closer scrutiny. The role of environmental factors is also coming under closer investigation. It is not clear yet whether environmental factors act merely as precipitating agents, always requiring an underlying genetic liability, or whether they represent an essential component of a pathogenetic process where genetic liability alone does not lead to the full-blown autism phenotype.