Autism: current theories regarding its pathogenesis and implications for rational pharmacotherapy

Autism is a pervasive developmental disorder that is aetiologically and clinically heterogeneous. Twin and family-genetic studies provide evidence for strong genetic components. An international consortium using an affected sib pair strategy has found a promising linkage to a region on chromosome 7. In 10 to 15% of cases autism is due to associated medical conditions that affect normal brain functioning. Postmortem studies on small case series report cellular abnormalities in the limbic system and cerebellum. Between 10 and 20% of individuals with autism have macrocephalia, which is in accordance with magnetic resonance imaging (MRI) findings of an increased total brain tissue volume and enlargement most prominent in the occipital and parietal lobes. The most robust and well replicated neurobiological abnormality in autism is an elevation of whole blood serotonin (5-hydroxytryptamine; 5-HT) found in over 30% of patients. Pharmacological interventions with serotonin reuptake inhibitors or with atypical neuroleptics that block both dopamine (D2) and serotonin (5-HT2) receptors seem to offer clinical benefit and merit further study.