Advancing a Neurodevelopmental Origin for Schizophrenia

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Abstract
A long-standing view has been that the study of the schizophrenic brain was the graveyard of neuropathologists.1 Not too many years ago, inconsistencies in postmortem reports of cellular neuropathology in schizophrenics led some to conclude that such efforts were premature. Both views have since been displaced by an avalanche of consistent structural and functional evidence of microscopic pathology in the frontal and temporal lobes of schizophrenics.2-11 Moreover, the morphologic validation of schizophrenic neuropathology has accelerated in the past decade with noninvasive methods to assess brain structure and function, establishing enlarged ventricles, reduced cortical gray matter, and hypometabolism of the frontal lobes and elements of the basal ganglia. Numerous examples have recently appeared in the ARCHIVES.12-19 The wealth of evidence attesting to a substantial neuropathology in schizophrenia leaves few doubters. Rather, the focus has turned to the issue of which changes are reproducible signs of the pathology and