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Postnatal Development of Prefrontal Inhibitory Circuits and the Pathophysiology of Cognitive Dysfunction in Schizophrenia

Authors


Address for correspondence: David A. Lewis, M.D., Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, W1651 BST, Pittsburgh, PA 15213. Voice: 412-624-3934; fax: 412-624-9910. lewisda@upmc.edu

Abstract

Abstract: The typical appearance of the clinical features of schizophrenia during late adolescence or early adulthood suggests that adolescence-related neurodevelopmental events may contribute to the pathophysiology of this disorder. Here the role that GABA-mediated inhibition in the dorsal lateral prefrontal cortex (DLPFC) plays in regulating working memory, a core cognitive process that matures late and that is disturbed in schizophrenia, is reviewed. Recent studies are summarized that demonstrate (1) that certain pre- and postsynaptic markers of GABA neurotransmission in the monkey DLPFC exhibit striking changes during adolescence, and (2) that these same markers are markedly altered in the DLPFC of subjects with schizophrenia. The implications of these findings for treatment and prevention strategies are discussed.

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