Abstract
Schizotypy phenotypes in the general population share etiopathogenic mechanisms and risk factors with schizophrenia, supporting the notion of psychosis as a continuum ranging from nonclinical to clinical deviance. Catechol-O-methyltransferase (COMT) is a candidate susceptibility gene for schizophrenia that is involved in the regulation of dopamine in the prefrontal cortex. Several recent studies have reported a sex difference in the impact of COMT genotype on psychiatric and cognitive phenotypes and personality traits. The present study investigated the association of COMT Val158Met (rs4680) with psychometric positive and negative schizotypy and psychotic experiences in a sample of 808 nonclinical young adults. The main finding was that sex moderates the association of COMT genotype with the negative dimension of both schizotypy and psychotic experiences. Male subjects carrying the Val allele tended to score higher on the negative dimension of both trait and symptom-like measures. The results from the present study are consistent with recent work suggesting an association between negative schizotypy and diminished prefrontal dopamine availability. They support the idea that a biological differentiation underlies the positive and negative schizotypy dimensions. Additionally, these findings contribute to the growing literature on sex-specific effects of COMT on the predisposition to psychiatric disorders and personality traits.
Highlights
Functional, clinical, and genetic epidemiological studies show that many parameters of brain function and structure vary between men and women [1]
The present study investigated the association of COMT Val158Met with psychometric positive and negative schizotypy and psychotic experiences in a sample of 808 nonclinical young adults
In the current study we tested the hypothesis that the functional polymorphism Val158Met in the COMT gene would be associated with the negative dimension of the psychosis proneness phenotype in a nonclinical sample
Summary
Functional, clinical, and genetic epidemiological studies show that many parameters of brain function and structure vary between men and women [1]. Most psychiatric disorders show sex differences in characteristics such as incidence, age at onset, clinical features, and outcome [2]. These differences are usually ascribed to the influence of sex hormones or the action of sex chromosome genes. Several lines of evidence suggest that the catechol-O-methyltransferase (COMT) gene, which codes for an enzyme that plays an important role in the cortical dopamine metabolism, may be one such gene. It contains a functional polymorphism, a G>A substitution (rs4680), which produces a valine-to-methionine (Val/Met) substitution that influences COMT activity in the human prefrontal cortex. It has been proposed that positive symptoms are due to a hyperactivity
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