Genetic variations in catechol-O-methyltransferase (COMT) modulate cortical dopamine levels and have been associated with various behavioral effects in humans and mice. Recent data also show gender differences. In this report, Sannino and colleagues report that genetically driven reduction in COMT enzyme activity is associated with increased cortical thickness in the prefrontal cortex (PFC) and postero-parieto-temporal cortex of male, but not female adult mice and humans. Reduced COMT activity was also associated with increased neuronal density in males, but reduced density 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. The authors suggest that gender-COMT gene interactions can modulate brain morphological substrates with influence on behavioral outcomes in healthy subjects and, potentially, in neuropsychiatric populations.
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 DR, Spalletta G, Papaleo F: COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and Humans. Cerebral Cortex [Epub ahead of print, March 21, 2014].
