Weder Natalie, Yang Bao Zhu, Douglas-Palumberi Heather, Massey Johari, Krystal John H, Gelernter Joel, Kaufman Joan
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA.
Biol Psychiatry. 2009 Mar 1;65(5):417-24. doi: 10.1016/j.biopsych.2008.09.013. Epub 2008 Nov 8.
Childhood adversity has been shown to interact with monoamine oxidase-A (MAOA) genotype to confer risk for antisocial behavior. Studies examining this gene-by-environment (G x E) association, however, have produced mixed results.
Relevant research is reviewed, and results of a study with 114 children (73 maltreated and 41 control subjects) are presented. The maltreated children represent the extreme on a continuum of adversity and were assessed at a time of extreme stress-shortly after removal from their parents' care due to abuse. Measures of aggressive behavior were obtained using standard research instruments, and monoamine oxidase-A MAOA genotypes were obtained from saliva-derived DNA specimens. Population structure was controlled for using ancestral proportion scores computed on the basis of genotypes of ancestry informative markers.
Many prior investigations appear to have had reduced power to detect the predicted G x E interaction because of low base rates of maltreatment and antisocial behavior in their samples and failure to use optimal procedures to control for population structure in ethnically diverse cohorts. In this investigation, a significant interaction was detected between exposure to moderate trauma and the "low-activity" MAOA genotype in conferring risk for aggression. Children with exposure to extreme levels of trauma, however, had high aggression scores regardless of genotype.
Our study suggests that problems in aggressive behavior in maltreated children are moderated by MAOA genotype, but only up to moderate levels of trauma exposure. Extreme levels of trauma appear to overshadow the effect of MAOA genotype, especially in children assessed at time of acute crisis.
童年期逆境已被证明与单胺氧化酶A(MAOA)基因型相互作用,从而增加反社会行为的风险。然而,研究这种基因-环境(G×E)关联的研究结果却喜忧参半。
回顾了相关研究,并展示了一项对114名儿童(73名受虐待儿童和41名对照儿童)的研究结果。受虐待儿童代表了逆境连续体上的极端情况,并且是在极端压力时期——因虐待行为而被从父母照料中带走后不久进行评估的。使用标准研究工具获得攻击性行为的测量数据,并从唾液衍生的DNA样本中获取单胺氧化酶A(MAOA)基因型。通过基于祖先信息标记的基因型计算的祖先比例分数来控制群体结构。
许多先前的调查似乎由于样本中虐待和反社会行为的低基础发生率,以及未能使用最佳程序来控制不同种族队列中的群体结构,而降低了检测预测的G×E相互作用的能力。在这项调查中,检测到中度创伤暴露与“低活性”MAOA基因型之间在赋予攻击风险方面存在显著相互作用。然而,暴露于极端创伤水平的儿童,无论基因型如何,攻击分数都很高。
我们的研究表明,受虐待儿童的攻击性行为问题受MAOA基因型的调节,但仅在中度创伤暴露水平内。极端水平的创伤似乎掩盖了MAOA基因型的影响,尤其是在急性危机时期接受评估的儿童中。