van Winkel Ruud, Henquet Cécile, Rosa Araceli, Papiol Sergi, Fananás Lourdes, De Hert Marc, Peuskens Jozef, van Os Jim, Myin-Germeys Inez
University Psychiatric Center Katholieke Universiteit Leuven, Leuvensesteenweg, Kortenberg, Belgium.
Am J Med Genet B Neuropsychiatr Genet. 2008 Jan 5;147B(1):10-7. doi: 10.1002/ajmg.b.30559.
Gene-environment interactions involving the catechol-O-methyltransferase Val(158)Met polymorphism (COMT(Val158Met)) have been implicated in the causation of psychosis. Evidence from general population studies suggests that Met/Met subjects are sensitive to stress, a trait associated with psychosis. We hypothesized that the Met allele would moderate the effects of stress on negative affect (NA) in controls, and on NA and psychosis in patients with a psychotic disorder. Thirty-one patients with a psychotic disorder and comorbid cannabis misuse and 25 healthy cannabis users were studied with the experience sampling method (ESM), a structured diary technique assessing current context and emotional and psychotic experiences in daily life. A significant interaction between COMT(Val158Met) genotype and ESM stress in the model of NA was found for patients (interaction chi(2) = 7.4, P = 0.02), but not for controls (interaction chi(2) = 3.8, P = 0.15). In the model of ESM psychosis, a significant interaction between COMT(Val158Met) genotype and ESM stress was also apparent (interaction chi(2) = 11.6, P < 0.01), with Met/Met patients showing the largest increase in psychotic experiences as well as NA in reaction to ESM stress. The findings suggest that the COMT(Val158Met) polymorphism moderates affective and psychotic responses to stress in patients with psychosis, providing evidence for gene-environment interaction mechanisms in the formation of psychotic symptoms.
涉及儿茶酚-O-甲基转移酶缬氨酸（158）蛋氨酸多态性（COMT（Val158Met））的基因-环境相互作用与精神病的病因有关。来自普通人群研究的证据表明，携带蛋氨酸/蛋氨酸基因型的个体对压力敏感，这是一种与精神病相关的特质。我们假设，蛋氨酸等位基因会调节压力对对照组负面情绪（NA）的影响，以及对患有精神障碍患者的负面情绪和精神病的影响。采用经验抽样法（ESM）对31名患有精神障碍且合并大麻滥用的患者和25名健康大麻使用者进行了研究，这是一种结构化日记技术，用于评估当前情境以及日常生活中的情绪和精神病体验。在患者的负面情绪模型中，发现COMT（Val158Met）基因型与ESM压力之间存在显著交互作用（交互卡方值=7.4，P=0.02），但在对照组中未发现（交互卡方值=3.8，P=0.15）。在ESM精神病模型中，COMT（Val158Met）基因型与ESM压力之间也存在显著交互作用（交互卡方值=11.6，P<0.01），携带蛋氨酸/蛋氨酸基因型的患者在对ESM压力的反应中，精神病体验以及负面情绪的增加最为明显。研究结果表明，COMT（Val158Met）多态性调节了精神病患者对压力的情感和精神病反应，为精神病症状形成中的基因-环境相互作用机制提供了证据。
