Cognitive Dysfunction in Schizophrenia
Convergence of  -Aminobutyric Acid and Glutamate Alterations
David A. Lewis, MD;
Bita Moghaddam, PhD
Arch Neurol. 2006;63:1372-1376.
Impairments in certain cognitive functions mediated by the dorsolateral prefrontal cortex, such as working memory, are core features of schizophrenia. Convergent findings suggest that these disturbances are associated with alterations in markers of inhibitory  -aminobutyric acid and excitatory glutamate neurotransmission in the dorsolateral prefrontal cortex. Specifically, reduced -aminobutyric acid synthesis is present in the subpopulation of -aminobutyric acid neurons that express the calcium-binding protein parvalbumin. Despite presynaptic and postsynaptic compensatory responses, the resulting impaired inhibitory regulation of pyramidal neurons contributes to a reduction in the synchronized neuronal activity that is required for working memory function. Several lines of evidence suggest that these changes may be either secondary to or exacerbated by impaired signaling via the N-methyl-D-aspartate class of glutamate receptors. These findings suggest specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.
Author Affiliations: Departments of Psychiatry and Neuroscience, University of Pittsburgh, Pittsburgh, Pa.
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