Three hypotheses for developmental defects that may... : Current Opinion in Neurology (original) (raw)

Developmental disorders: Edited by Geraldine Dawson

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

Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, Center for Neurobiology and Psychiatry, Rock Hall, Room RH 284C, UCSF MC 2611, University of California at San Francisco, San Francisco, California, USA

Correspondence to John L.R. Rubenstein, MD, PhD, Nina Ireland Laboratory of Developmental Neurobiology, Center for Neurobiology and Psychiatry, Department of Psychiatry, Rock Hall, Room RH 284C, UCSF MC 2611, 1550 4th Street, University of California at San Francisco, San Francisco, CA 94158-2324, USA Tel: +1 415 476 7862; fax: +1 415 476 7884; e-mail: [email protected]

Abstract

Purpose of review

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.

Recent findings

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.

Summary

Understanding these mechanisms opens the possibility to therapeutic interventions.