COMT and schizophrenia: Numerous preclinical studies support that the DAergic system is one of the key mediators of sex differences in schizophrenia (Bay-Richter et al., 2009; Arime et al., 2012; for a detailed presentation of this issue, see Sanchez et al., 2010); accordingly, genetic investigations point to a clear involvement of the key metabolic enzymes of DA, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), in the underpinnings of G×S interactions in schizophrenia.