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

Sannino, Sara and Gozzi, Alessandro and Cerasa, Antonio and Piras, Fabrizio and Scheggia, Diego and Manago, Francesca and Damiano, Mario and Galbusera, Alberto and Erickson, Lucy C. and De Pietri Tonelli, Davide and Bifone, Angelo and Tsaftaris, Sotirios A. and Caltagirone, Carlo and Weinberger, Daniel R. and Spalletta, Gianfranco and Papaleo, Francesco COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and Humans. Cerebral Cortex, 25 (9). pp. 2529-2541. ISSN 1047-3211 (2015)

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Genetic 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.

Item Type: Article
Identification Number: 10.1093/cercor/bhu053
Additional Information: First published online: March 21, 2014
Uncontrolled Keywords: cognition ; cortical thickness ; dopamine ; postero-parietal cortex ; prefrontal cortex
Subjects: Q Science > QA Mathematics > QA75 Electronic computers. Computer science
R Medicine > R Medicine (General)
Research Area: Computer Science and Applications
Depositing User: Ms T. Iannizzi
Date Deposited: 27 Mar 2014 09:30
Last Modified: 05 Apr 2016 12:01
URI: http://eprints.imtlucca.it/id/eprint/2182

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