• Cerebral cortex · Sep 2015

    COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and Humans.

    • Sara Sannino, Alessandro Gozzi, Antonio Cerasa, Fabrizio Piras, Diego Scheggia, Francesca Managò, Mario Damiano, Alberto Galbusera, Lucy C Erickson, Davide De Pietri Tonelli, Angelo Bifone, Sotirios A Tsaftaris, Carlo Caltagirone, Daniel R Weinberger, Gianfranco Spalletta, and Francesco Papaleo.
    • Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
    • Cereb. Cortex. 2015 Sep 1; 25 (9): 2529-41.

    AbstractGenetic variations in catechol-O-methyltransferase (COMT) that modulate cortical dopamine have been associated with pleiotropic behavioral effects in humans and mice. Recent data suggest that some of these effects may vary among sexes. However, the specific brain substrates underlying COMT sexual dimorphisms remain unknown. Here, we report that genetically driven reduction in COMT enzyme activity increased cortical thickness in the prefrontal cortex (PFC) and postero-parieto-temporal cortex of male, but not female adult mice and humans. Dichotomous changes in PFC cytoarchitecture were also observed: reduced COMT increased a measure of neuronal density in males, while reducing it in female mice. Consistent with the neuroanatomical findings, COMT-dependent sex-specific morphological brain changes were paralleled by divergent effects on PFC-dependent working memory in both mice and humans. These findings emphasize a specific sex-gene interaction that can modulate brain morphological substrates with influence on behavioral outcomes in healthy subjects and, potentially, in neuropsychiatric populations.© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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