Feature Finding Title
Featured Finding Figure
Postmortem studies have revealed reduced densities of dendritic spines in the dorsal lateral prefrontal cortex (DLPFC) of subjects with schizophrenia. However, the molecular mechanisms that might contribute to these alterations are unknown. Recent studies of the intracellular signals that regulate spine dynamics have identified members of the RhoGTPase family (e.g., Cdc42, Rac1, RhoA) as critical regulators of spine structure. In addition, Duo and drebrin are spine-specific proteins that are critical for spine maintenance and spine formation, respectively. In order to determine whether the mRNA expression levels of Cdc42, Rac1, RhoA, Duo or drebrin are altered in schizophrenia, tissue sections containing DLPFC area 9 from 15 matched pairs of subjects with schizophrenia and control subjects were processed for in situ hybridization. As shown in the figure, expression levels of each mRNA were reduced in a schizophrenia subject compared to a matched control. Quantitative studies confirmed reduced expression of each of these mRNAs in the gray matter of the subjects with schizophrenia compared to the control subjects, although only the reductions in Cdc42 and Duo remained significant after corrections for multiple comparisons. In addition, spine density was strongly correlated with the expression levels of both Duo (r = 0.73, p= .007) and Cdc42 (r = 0.71, p = .009) mRNAs. In contrast, the expression levels of Cdc42 and Duo mRNAs were not altered in monkeys chronically exposed to the antipsychotic medications haloperidol or olanzapine. In conclusion, reduced expression of Cdc42 and Duo mRNAs may represent molecular mechanisms that contribute to the decreased density of dendritic spines in the DLPFC of subjects with schizophrenia.
Justin J. Hill, Takanori Hashimoto and David A. Lewis: Molecular Mechanisms Contributing to Dendritic Spine Alterations in the Prefrontal Cortex of Subjects with Schizophrenia. Molecular Psychiatry 11: 557-566, 2006.

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