Evans Jonathan, Xu Ke, Heron Jon, Enoch Mary-Anne, Araya Ricardo, Lewis Glyn, Timpson Nic, Davies Simon, Nutt David, Goldman David
University of Bristol, Cotham Hill, UK.
Am J Med Genet B Neuropsychiatr Genet. 2009 Mar 5;150B(2):209-18. doi: 10.1002/ajmg.b.30789.
Early adversity predicts anxiety and depression but variation in response to adversity is not understood. We investigated whether association between early adversity and emotional symptoms in young children differs according to variation of the COMT gene. The main outcome measure was the emotionality subscale of the Strengths and Difficulties Questionnaire (SDQ) completed by mothers for 8,431 children aged 6-7 years old in the Avon Longitudinal Study of Parents and Children. Adversity measures included exposure to maternal postpartum depressive symptoms and adverse life events for children. DNA from the children was genotyped for five COMT polymorphisms including the COMT Val158Met locus. Maternal depression increased the odds of high emotionality in the children, (OR 1.99, 95% CI 1.73-2.29, P < 0.001) as did life events score, (OR 1.21 for each s.d. increase in life event score, 95% CI 1.15-1.27, P < 0.001). There was no main effect of Val158Met genotype on emotional symptoms (OR for effect of each copy of the methionine allele was 1.04, 95% CI 0.97-1.10, P = 0.284). The relationship between adversity and emotional symptoms did not vary by genotype (G x E for maternal depression chi(2) = 3.17, P = 0.205; G x E for life events chi(2) = 1.69, P = 0.430). There was no main effect of COMT haplotype, nor was there an interaction with adversity. Early adversity predicts emotional symptoms in children aged 6-7 years. Although some studies indicate a role for COMT in emotionality, anxiety, and depression in adults, no direct effect or interaction of COMT genotype was observed in this large sample of young children.
早期逆境预示着焦虑和抑郁,但人们对逆境反应的个体差异尚不清楚。我们调查了幼儿早期逆境与情绪症状之间的关联是否因儿茶酚-O-甲基转移酶(COMT)基因的变异而有所不同。主要的结局指标是在阿冯父母与儿童纵向研究中,母亲们为8431名6至7岁儿童填写的长处与困难问卷(SDQ)中的情绪性分量表。逆境测量包括儿童暴露于母亲产后抑郁症状和不良生活事件。对儿童的DNA进行基因分型,检测包括COMT Val158Met位点在内的5种COMT基因多态性。母亲抑郁会增加儿童出现高情绪性的几率(比值比1.99,95%置信区间1.73 - 2.29,P < 0.001),生活事件得分也是如此(生活事件得分每增加一个标准差,比值比为1.21,95%置信区间1.15 - 1.27,P < 0.001)。Val158Met基因型对情绪症状没有主要影响(甲硫氨酸等位基因每一份拷贝的效应比值比为1.04,95%置信区间0.97 - 1.10,P = 0.284)。逆境与情绪症状之间的关系不会因基因型而有所不同(母亲抑郁的基因 - 环境交互作用χ² = 3.17,P = 0.205;生活事件的基因 - 环境交互作用χ² = 1.69,P = 0.430)。COMT单倍型没有主要影响,也不存在与逆境的交互作用。早期逆境可预测6至7岁儿童的情绪症状。尽管一些研究表明COMT在成年人的情绪性、焦虑和抑郁中起作用,但在这个大量幼儿样本中未观察到COMT基因型的直接效应或交互作用。