Schizophrenia as a disorder of neurodevelopment.
A combination of genetic susceptibility and environmental perturbations appear to be necessary for the expression of schizophrenia. In addition, the pathogenesis of the disease is hypothesized to be neurodevelopmental in nature based on reports of an excess of adverse events during the pre- and perinatal periods, the presence of cognitive and behavioral signs during childhood and adolescence, and the lack of evidence of a neurodegenerative process in most individuals with schizophrenia. Recent studies of neurodevelopmental mechanisms strongly suggest that no single gene or factor is responsible for driving a highly complex biological process. Together, these findings suggest that combinatorial genetic and environmental factors, which disturb a normal developmental course early in life, result in molecular and histogenic responses that cumulatively lead to different developmental trajectories and the clinical phenotype recognized as schizophrenia.
Lewis
David A
DA
Department of Psychiatry, University of Pittsburgh School of Medicine, University of Pittsburgh, Pennsylvania 15213, USA. lewisda@msx.upmc.edu
Levitt
Pat
P
D000293:Adolescent; D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008959:Models, Neurological; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology