Evidence that the COMT Val158Met polymorphism moderates subclinical psychotic and affective symptoms in unaffected first-degree relatives of patients with schizophrenia

Abstract: Objectives: Psychotic patients with COMT Val158Met Met alleles were recently found to display more intense psychotic and affective responses to daily life stressors. We aimed to test the hypothesis that the Met allele is implicated in the development of affective and psychotic symptomatology in subjects genetically at risk for schizophrenia, by testing if unaffected first-degree relatives of patients with schizophrenia who share a Met allele have greater concordance of symptomatology than relatives not sharing a Met allele. Methods: Unaffected relatives (n =38) were arranged in as many genetically related pairs as possible (n =26), and Met-sharing between Index Unaffected Subject (IUS) and Related Unaffected Subject (RUS) was assessed. Symptomatology was assessed with the Brief Psychiatric Rating Scale (BPRS) total score. Results: Multilevel regression revealed an interaction between RUS BPRS score and Met-sharing in the model of IUS BPRS score (interaction χ 2 =3.78, p =0.05). Stratified analyses revealed that IUS–RUS total BPRS scores were significantly associated in the case of Met-sharing (B =0.57, 95% CI: 0.22–0.93, p =0.002), but were not when there was no Met-sharing. Conclusion: These findings support the hypothesis that the Met allele may be involved in the causation of psychopathology, at least in populations with a genetic predisposition to psychosis. [Copyright &y& Elsevier]