Association between the COMT Val158Met polymorphism and aggression in psychosis: Test of a moderated mediation model in a forensic inpatient sample

Objective: Aggression in schizophrenia can be explained by at least 2 different pathways. One of these pathways is aggression associated with comorbid antisocial characteristics. This pathway of aggressive behavior is likely to have a distinct underlying etiology, including particular genetic underpinnings. The Val allele of the COMT Val158Met polymorphism is found to be related to some forms of antisocial characteristics. This study aimed to examine the relation between the Val allele of the COMT Val158Met polymorphism and antisocial characteristics in forensic inpatients with a psychotic disorder and without a psychotic disorder. It was hypothesized that the relation between the Val allele and aggression would be mediated by diminished cognitive control (i.e., disinhibition). Method: A final sample of 71 male forensic inpatients were included and genotyped for the val158met SNP of the COMT gene. Self-reported aggression was measured with the Reactive-Proactive Aggression Questionnaire and different constructs of psychopathic traits (i.e., boldness, meanness and disinhibition) were measured using the Triarchic Psychopathy Measure. Results: Results showed that the Val allele was positively related to aggression and disinhibition in a subsample of patients with a psychotic disorder. Moreover, the relation between the Val allele and aggression in this subsample was conditionally mediated by disinhibition. Conclusion: These results indicate that aggression posed by patients with a psychotic disorder can be explained by different neurobiological pathways, 1 of which associated with a dysfunctional working of inhibitory control (i.e., disinhibition). These outcomes highlight the importance of personalized forensic treatment for specific subgroups of offenders with psychosis.

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