Sex-dichotomous effects of functional COMT genetic variations on cognitive functions disappear after menopause in both health and schizophrenia

Francesco Papaleo, Sara Sannino, Fabrizio Piras, Gianfranco Spalletta

Research output: Contribution to journalArticle

Abstract

Different genetic variations in the catechol-O-methyltransferase (COMT) gene have been indicated to functionally regulate the encoded enzyme. Despite the vast literature on the single nucleotide COMT ValMet polymorphism, the impact of complex haplotypes on cognitive functions has been overlooked. Here we contrasted the effects of complex COMT haplotypes with the ValMet polymorphism on cognitive functions and their interaction with menopause, in healthy subjects and patients with schizophrenia. Healthy adults (N=229) as well as patients with schizophrenia (N=172) underwent a comprehensive cognitive assessment taking into account the menopausal state. Functional COMT variations selectively modulated working memory and executive functions. Strikingly, these effects were present only in adult men but not in women before menopause, in both healthy subjects and patients with schizophrenia. Importantly, the same pattern of COMT-dependent effects present in men reappeared in women after menopause. Thus, functional COMT mutations seem to modulate cognitive functions depending on the hormonal status. These data clarify the importance of taking into account the combined effect of sex, hormonal status and genetics.

Original languageEnglish
Pages (from-to)2349-2363
Number of pages15
JournalEuropean Neuropsychopharmacology
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

Keywords

  • Cognition
  • Executive functions
  • Gene mutations
  • Haplotypes
  • Hormonal status
  • Psychiatry

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology

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