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 Weinberger, Gianfranco Spalletta, Francesco Papaleo

Research output: Contribution to journalArticle

Abstract

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 sexspecific 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.

Original languageEnglish (US)
Pages (from-to)2529-2541
Number of pages13
JournalCerebral Cortex
Volume25
Issue number9
DOIs
StatePublished - Sep 1 2015

Fingerprint

Catechol O-Methyltransferase
Short-Term Memory
Anatomy
Prefrontal Cortex
Brain
Temporal Lobe
Sex Characteristics
Dopamine
Healthy Volunteers
Enzymes
Population
Genes

Keywords

  • Cognition
  • Cortical thickness
  • Dopamine
  • Postero-parietal cortex
  • Prefrontal cortex

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Sannino, S., Gozzi, A., Cerasa, A., Piras, F., Scheggia, D., Managò, F., ... Papaleo, F. (2015). COMT genetic reduction produces sexually divergent effects on cortical anatomy and working memory in mice and humans. Cerebral Cortex, 25(9), 2529-2541. https://doi.org/10.1093/cercor/bhu053

COMT genetic reduction produces sexually divergent effects on cortical anatomy and working memory in mice and humans. / Sannino, Sara; Gozzi, Alessandro; Cerasa, Antonio; Piras, Fabrizio; Scheggia, Diego; Managò, Francesca; Damiano, Mario; Galbusera, Alberto; Erickson, Lucy C.; De Pietri Tonelli, Davide; Bifone, Angelo; Tsaftaris, Sotirios A.; Caltagirone, Carlo; Weinberger, Daniel; Spalletta, Gianfranco; Papaleo, Francesco.

In: Cerebral Cortex, Vol. 25, No. 9, 01.09.2015, p. 2529-2541.

Research output: Contribution to journalArticle

Sannino, S, Gozzi, A, Cerasa, A, Piras, F, Scheggia, D, Managò, F, Damiano, M, Galbusera, A, Erickson, LC, De Pietri Tonelli, D, Bifone, A, Tsaftaris, SA, Caltagirone, C, Weinberger, D, Spalletta, G & Papaleo, F 2015, 'COMT genetic reduction produces sexually divergent effects on cortical anatomy and working memory in mice and humans', Cerebral Cortex, vol. 25, no. 9, pp. 2529-2541. https://doi.org/10.1093/cercor/bhu053
Sannino, Sara ; Gozzi, Alessandro ; Cerasa, Antonio ; Piras, Fabrizio ; Scheggia, Diego ; Managò, Francesca ; Damiano, Mario ; Galbusera, Alberto ; Erickson, Lucy C. ; De Pietri Tonelli, Davide ; Bifone, Angelo ; Tsaftaris, Sotirios A. ; Caltagirone, Carlo ; Weinberger, Daniel ; Spalletta, Gianfranco ; Papaleo, Francesco. / COMT genetic reduction produces sexually divergent effects on cortical anatomy and working memory in mice and humans. In: Cerebral Cortex. 2015 ; Vol. 25, No. 9. pp. 2529-2541.
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