RESUMO
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 chi(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.
Assuntos
Catecol O-Metiltransferase/genética , Genótipo , Metionina/genética , Polimorfismo Genético/genética , Transtornos Psicóticos/genética , Esquizofrenia/genética , Valina/genética , Adulto , Escalas de Graduação Psiquiátrica Breve , Feminino , Predisposição Genética para Doença/genética , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Fatores de Risco , Esquizofrenia/diagnósticoRESUMO
BACKGROUND: Previous work suggests that reaction time variability (RTV) in attentional tasks, as a measure of cognitive stability, is associated with degree of Val loading in COMT Val(158)Met genotype, and that this association may be relevant for the aetiology of schizophrenia. This study examined (i) to what degree RTV pertaining to tasks of varying cognitive complexity would be associated with increased risk for schizophrenia and (ii) to what degree this would be mediated by Val loading. METHODS: COMT genotyping was investigated in a sample of 23 patients with schizophrenia, 33 first-degree relatives, and 21 controls. All participants performed the Flanker continuous performance test. RESULTS: Schizophrenia liability was associated with number of correct trials of the Flanker test, but not with RTV, and this association was not mediated by COMT Val(158)Met genotype. Similarly, Met loading was associated with number of correct trials and with RTV, but this was not mediated by schizophrenia liability. CONCLUSIONS: Associations between COMT Val(158)Met genotype and RTV do not appear to reflect transmission of schizophrenia liability in families. Differential associations with Val and Met alleles across studies suggest indirect effects through gene-gene interactions or the influence of a functional polymorphism near COMT Val(158)Met.
