title: Gene-sex interactions in schizophrenia: focus on dopamine neurotransmission.
abstract: Schizophrenia is a severe mental disorder, with a highly complex and heterogenous clinical presentation. Our current perspectives posit that the pathogenic mechanisms of this illness lie in complex arrays of gene × environment interactions. Furthermore, several findings indicate that males have a higher susceptibility for schizophrenia, with earlier age of onset and overall poorer clinical prognosis. Based on these premises, several authors have recently begun exploring the possibility that the greater schizophrenia vulnerability in males may reflect specific gene × sex (G×S) interactions. Our knowledge on such G×S interactions in schizophrenia is still rudimentary; nevertheless, the bulk of preclinical evidence suggests that the molecular mechanisms for such interactions are likely contributed by the neurobiological effects of sex steroids on dopamine (DA) neurotransmission. Accordingly, several recent studies suggest a gender-specific association of certain DAergic genes with schizophrenia. These G×S interactions have been particularly documented for catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), the main enzymes catalyzing DA metabolism. In the present review, we will outline the current evidence on the interactions of DA-related genes and sex-related factors, and discuss the potential molecular substrates that may mediate their cooperative actions in schizophrenia pathogenesis.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas Lawrence, KS, USA.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Godar
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas Lawrence, KS, USA ; Consortium for Translational Research on Aggression and Drug Abuse, University of Kansas Lawrence, KS, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Bortolato
keywords: catecholamine-O-methyltransferase (COMT); dopamine; gene-sex interactions; monoamine oxidase (MAO); schizophrenia; sex hormones