Title - Feature Finding
Featured Finding Figure
Alterations in the inhibitory circuitry of the dorsolateral prefrontal cortex (DLPFC) in schizophrenia include reduced expression of the mRNA for somatostatin (SST), a neuropeptide present in a subpopulation of GABA neurons. However, neither the cellular substrate nor the causal mechanisms for decreased SST mRNA levels in schizophrenia are known. We used in situ hybridization to quantify the compartmental, laminar, and cellular levels of SST mRNA expression in the DLPFC of 23 pairs of schizophrenia and control subjects. We also explored potential causal mechanisms by utilizing similar methods to analyze SST mRNA expression in several animal models. The expression of SST mRNA was significantly decreased in layers 2 - superficial 6 of subjects with schizophrenia, but not in layer 1, deep 6 or the white matter. At the cellular level, both the density of cortical SST mRNA-positive neurons and the expression of SST mRNA per neuron were reduced in the subjects with schizophrenia. These alterations were not due to potential confounds and appeared to be a down-stream consequence of impaired neurotrophin signaling through the trkB receptor. For example, as shown in the figure, the expression of SST mRNA in the prefrontal cortex of mice declined in association with genetically-engineered reductions in trkB mRNA expression driven by the fB2 locus. These findings support the hypothesis that a marked reduction in SST mRNA expression in a subset of GABA neurons contributes to DLPFC dysfunction in schizophrenia.
Morris H, Hashimoto T, Lewis DA: Alterations in somatostatin mRNA expression in the dorsolateral prefrontal cortex of subjects with schizophrenia. Cerebral Cortex 18: 1575-1587, 2008.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
3811 O'Hara Street, Biomedical Science Tower W1654
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