Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
PLoS One. 2012;7(6):e39709. doi: 10.1371/journal.pone.0039709. Epub 2012 Jun 22.
The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT) gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.
情绪相关障碍（如焦虑或情感障碍）的病因被认为是复杂的，涉及生物和环境因素的相互作用。部分证据表明，多巴胺能和去甲肾上腺素能系统发生改变——部分归因于儿茶酚氧位甲基转移酶（COMT）基因变异——以及腺苷能系统和早期生活创伤构成了这些疾病的风险因素。采用多水平方法，在 95 名健康成年人的样本中，我们研究了功能性 COMT Val158Met 多态性、咖啡因（作为腺苷 A2A 受体拮抗剂，在安慰剂对照干预设计中为 300mg）以及童年期创伤（CTQ）的影响，以及它们对情绪调节的惊吓反应的相互作用，作为一种潜在与恐惧和痛苦相关障碍相关的神经生物学防御反射。COMT val/val 基因型显著增加了对不愉快刺激的惊吓幅度，而 met/met 纯合子对厌恶图片的惊吓反应则减弱。此外，还发现 COMT Val158Met 基因型与 CTQ 的显著基因-环境相互作用，在 val/val 受试者中，更多的创伤与更高的惊吓增强相关，但在 met 携带者中则没有。未观察到咖啡因的主要作用或与咖啡因的相互作用。结果表明，COMT Val158Met 变体和童年期创伤对情绪调节的惊吓反射既有主要作用，也有 GxE 作用，支持情绪调节的惊吓反射作为一种潜在与焦虑和情感障碍相关的基本神经生物学防御反射的复杂发病模型。
