Neurodevelopmental Theories of Schizophrenia: Twenty‐First Century Perspectives

Abstract

Schizophrenia is a devastating mental illness afflicting about 1 percent of the population, involving delusions and hallucinations. Although originally believed to be a disorder of neurodegeneration, multiple lines of inquiry now provide compelling evidence for its neurodevelopmental origins. As such, one of the most puzzling aspects about this disorder is its characteristic onset in late adolescence or early adulthood. In this chapter we review evidence for the involvement of both early (genetic and perinatal) and later (adolescent) neurodevelopmental influences in the etiology and pathogenesis of schizophrenia. New findings regarding its genetic architecture implicate both common and rare genetic variants that converge on pathways involving disruption of synaptic plasticity, which may be related to neural endophenotypes present in both patients and their clinically unaffected relatives. Together, these findings suggest a combination of these early and later neurodevelopmental factors converge to produce the cellular, structural, and functional deficits underlying the disorder.