Feature Finding Title
Featured Finding Figure
Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC) result, at least in part, from abnormalities in GABA neurotransmission as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, in this study we sought to determine whether this pattern of altered gene expression is restricted to the DLPFC or could also contribute to the dysfunction of other cortical areas in the illness. Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (DLPFC, anterior cingulate, primary motor and primary visual cortices) from 12 subjects with schizophrenia and matched normal comparison subjects. Expression levels of seven transcripts were lower in the subjects with schizophrenia with the magnitude of the reductions for each transcript indistinguishable across the four areas (Figure). The largest reductions were detected for the mRNAs encoding somatostatin (SST) and parvalbumin (PV), followed by moderate decreases in mRNA expression for the 67 kD isoform of glutamate decarboxylase (GAD67), the GABA membrane transporter 1 (GAT1), and the α1 and δ subunits of GABAA receptors. In contrast, the expression of calretinin (CR) mRNA did not differ between the subject groups in any of the four areas. Because the areas examined represent the major functional domains (e.g., association, limbic, motor and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contributes to the pathophysiology of different clinical features of schizophrenia.
Takanori Hashimoto, H Holly Bazmi, Karoly Mirnics, Qiang Wu, Allan R Sampson, and David A Lewis: Conserved Regional Patterns of GABA-Related Transcript Expression in the Neocortex of Subjects with Schizophrenia. Am J Psychiatry 165: 479-489, 2008.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
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