Sex-dependent effect on the association of COMT Val158Met polymorphism with schizophrenia clinical symptoms and cognitive impairment

Abstract Catechol-O-methyltransferase (COMT) Val158Met (rs4680) polymorphism is thought to be involved in the pathogenesis of schizophrenia, which is related to the regulation of dopamine transmission in the prefrontal cortex. Recent studies have shown that the influence of COMT Val158Met variation is sexually dimorphic. This study aims to explore the possible effect of the interaction between COMT Val158Met polymorphism and sex on patients’ clinical characteristics and cognitive function. 367 inpatients with chronic schizophrenia (246 males and 121 females) and 419 healthy controls (172 males and 247 females) are recruited. The cognitive performances are assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the COMT Val158Met polymorphism is genotyped. The psychopathological symptoms of the patients are assessed by the Positive and Negative Syndrome Scale (PANSS). We find that: 1) sex difference in the allele frequency and genotype distribution of COMT Val158Met are found only in schizophrenia patients; 2) there is sex × COMT genotype interaction in positive symptoms, immediate memory, attention, and RBANS total score indexes in patients with schizophrenia; 3) mainly in the male patients’ sample, Val/Val carriers exhibit more positive symptoms and more severe cognitive impairment than Met carriers. These findings suggest that COMT Val158Met polymorphism is associated with the risk and severity of schizophrenia in a sexually dimorphic way, which is helpful to understand the factors that may lead to different manifestations of male and female patients with schizophrenia.