Development and Psychopathology

Reflecting on the Past and Planning for the Future of Developmental Psychopathology

The neurodevelopmental hypothesis of schizophrenia: Following a trail of evidence from cradle to grave

a1 Clinical Brain Disorders Branch, IRP, NIMH, NIH


This is a critical review of the literature related to the neurodevelopmental hypothesis of schizophrenia which posits that the illness is related to abnormal brain development. The review focuses on data deriving from clinical studies, and it is organized according to the life phase from which the data were collected: conception and birth, infancy and childhood up to the onset of the illness, after illness onset, and postmortem. The neurodevelopmental hypothesis is supported by several pieces of evidence, including increased frequency of obstetric complications in patients with schizophrenia; the presence of minor physical anomalies; the presence of neurological, cognitive, and behavioral dysfunction long before illness onset; a course and outcome of the illness itself that is incompatible in most cases with a degenerative illness; the stability of brain structural measures over time; and the absence of postmortem evidence of neurodegeneration. A historical perspective on how this research accumulated and a section addressing important areas of future investigation are also provided. We conclude that schizophrenia is certainly not a degenerative brain disorder, and that it is likely that a brain insult in utero or at birth plays a role in its expression. Current evidence cannot completely exclude the role of environmental variables after birth. In addition, it is possible that other psychiatric disorders may also have a neurodevelopmental component.

c1 Address correspondence and reprint requests to: Daniel R. Weinberger, MD, CBDB/NIMH/NIH, Building 10, 4S235, 9000 Rockville Pike, Bethesda, MD 20892;