Araya Ricardo, Hu Xianzhang, Heron Jon, Enoch Mary-Anne, Evans Jonathan, Lewis Glyn, Nutt David, Goldman David
University of Bristol, United Kingdom.
Am J Med Genet B Neuropsychiatr Genet. 2009 Jul 5;150B(5):670-82. doi: 10.1002/ajmg.b.30888.
There has been a large but inconsistent literature on interactions between the 5-HTTLPR polymorphism of the serotonin transporter gene and adversity on emotional disorders. We investigated these interactions in 4,334 children from a birth longitudinal cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). We measured emotional symptoms at 7 years with the Strengths and Difficulties Questionnaire. Mothers rated stressful life events between ages 5 and 7 years. Maternal depression was defined as a score > or =12 on the Edinburgh Postnatal Depression Scale at 2 or 8 months postnatally. Triallelic genoptyping of the 5-HTTLPR polymorphism was performed. We found strong associations between stressful life events (OR 1.19; 1.12-1.26; P < 0.01) and maternal postnatal depression (OR 1.91; 1.63-2.24; P < 0.01) with emotional symptoms in the children. There were no main 5-HTTLPR genotype effects or significant interactions between genotype and life events or maternal postnatal depression on emotional symptoms. There was marginal evidence (P = 0.08) for an interaction between stressful life events and genotype in boys only, with those in the low and high 5-HTTLPR expression groups showing stronger associations. In these 7-year-old children, we did not replicate previously reported G x E interactions between 5-HTTLPR and life events for emotional symptoms. Gene by environment interactions may be developmentally dependent and show variation depending on the type and levels of exposure and sex. Young cohorts are essential to improve our understanding of the impact of development on gene and environment interactions.
关于血清素转运体基因的5-HTTLPR多态性与情绪障碍方面的逆境之间的相互作用,已有大量但不一致的文献报道。我们在一个出生队列研究的4334名儿童中调查了这些相互作用:阿冯父母与儿童纵向研究(ALSPAC)。我们在7岁时用长处和困难问卷测量情绪症状。母亲们对5至7岁之间的应激性生活事件进行评分。产后抑郁症定义为产后2个月或8个月时在爱丁堡产后抑郁量表上的得分≥12分。对5-HTTLPR多态性进行了三等位基因基因分型。我们发现应激性生活事件(比值比1.19;1.12 - 1.26;P < 0.01)和母亲产后抑郁症(比值比1.91;1.63 - 2.24;P < 0.01)与儿童的情绪症状之间存在强烈关联。5-HTTLPR基因型没有主要效应,基因型与生活事件或母亲产后抑郁症之间在情绪症状上也没有显著相互作用。仅在男孩中存在应激性生活事件与基因型之间相互作用的边际证据(P = 0.08),5-HTTLPR低表达组和高表达组的男孩显示出更强的关联。在这些7岁儿童中,我们没有重复先前报道的5-HTTLPR与生活事件之间关于情绪症状的基因×环境相互作用。基因与环境的相互作用可能在发育上具有依赖性,并根据暴露类型和水平以及性别而有所变化。年轻队列对于提高我们对发育对基因与环境相互作用影响的理解至关重要。