title: Postnatal development of prefrontal inhibitory circuits and the pathophysiology of cognitive dysfunction in schizophrenia.
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.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, W1651 BST, Pittsburgh, PA 15213, USA. lewisda@upmc.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
authors.forename: Dianne
authors.initials: D
authors.lastname: Cruz
authors.forename: Stephen
authors.initials: S
authors.lastname: Eggan
authors.forename: Susan
authors.initials: S
authors.lastname: Erickson
mesh_terms: D000293:Adolescent; D000818:Animals; D003072:Cognition Disorders / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D009433:Neural Inhibition / Q000502:physiology; D016571:Neural Networks, Computer; D009434:Neural Pathways / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D017397:Prefrontal Cortex / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D012559:Schizophrenia / Q000473:pathology / Q000503:physiopathology*; D013569:Synapses / Q000473:pathology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid