Three hypotheses for developmental defects that may underlie some forms of autism spectrum disorder

Molecular and genetic insights into the etiology of autism spectrum disorders are now available. The field now needs to understand how these perturbations affect development and function of the brain. Herein I review the genetic mechanisms known to predispose to autism spectrum disorders, and attempt to consolidate many of these within cellular/molecular pathways that regulate development of neural systems that underlie cognition and social behaviors. In addition to the clear relationship of many susceptibility genes to activity-dependent neural responses, I propose the existence of three additional mechanisms that may contribute to autism spectrum disorders: evolutionary-driven expansion of cerebrum and cerebellar size; imbalance in the excitatory/inhibitory ratio in local and extended circuits; the hormonal effects of the male genotype. Understanding these mechanisms opens the possibility to therapeutic interventions.