title: Sex-dichotomous effects of functional COMT genetic variations on cognitive functions disappear after menopause in both health and schizophrenia.
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.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genova, Italy. Electronic address: francesco.papaleo@iit.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Papaleo
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Sannino
authors.affiliation: IRCCS Santa Lucia Foundation, Neuropsychiatry Laboratory, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Piras
authors.affiliation: IRCCS Santa Lucia Foundation, Neuropsychiatry Laboratory, Rome, Italy; Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008593:Menopause; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications*; D012565:Schizophrenic Psychology
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Cognition; Executive functions; Gene mutations; Haplotypes; Hormonal status; Psychiatry