Kendler K S, Kessler R C, Walters E E, MacLean C, Neale M C, Heath A C, Eaves L J
Department of Psychiatry, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0710, USA.
Am J Psychiatry. 1995 Jun;152(6):833-42. doi: 10.1176/ajp.152.6.833.
This study was undertaken to clarify how genetic liability and stressful life events interact in the etiology of major depression.
Information about stressful life events and onset of major depressive episodes in the past year was collected in a population-based sample of female-female twin pairs including 2,164 individuals, 53,215 person-months of observation, and 492 onsets of depression.
Nine "personal" and three aggregate "network" stressful events significantly predicted onset of major depression in the month of occurrence, four of which predicted onset with an odds ratio of > 10 and were termed "severe": death of a close relative, assault, serious marital problems, and divorce/breakup. Genetic liability also had a significant impact on risk of onset of depression. For severe stressful events, as well as for 10 of the 12 individual stressful events, the best-fitting model for the joint effect of stressful events and genetic liability on onset of major depression suggested genetic control of sensitivity to the depression-inducing effects of stressful life events. In individuals at lowest genetic risk (monozygotic twin, co-twin unaffected), the probability of onset of major depression per month was predicted to be 0.5% and 6.2%, respectively, for those unexposed and exposed to a severe event. In those at highest genetic risk (monozygotic twin, co-twin affected), these probabilities were 1.1% and 14.6%, respectively. Linear regression analysis indicated significant Genotype by Environment interaction in the prediction of onset of major depression.
Genetic factors influence the risk of onset of major depression in part by altering the sensitivity of individuals to the depression-inducing effect of stressful life events.
本研究旨在阐明遗传易感性与应激性生活事件在重度抑郁症病因学中是如何相互作用的。
在一个基于人群的女性双胞胎样本中收集了过去一年中应激性生活事件和重度抑郁发作的信息，该样本包括2164名个体、53215人月的观察期以及492次抑郁发作。
九种“个人”和三种总体“网络”应激事件显著预测了重度抑郁症在发生当月的发作，其中四种事件预测发作的优势比>10，被称为“严重”事件：近亲死亡、袭击、严重婚姻问题和离婚/分手。遗传易感性也对抑郁症发作风险有显著影响。对于严重应激事件以及12种个体应激事件中的10种，应激事件和遗传易感性对重度抑郁症发作的联合效应的最佳拟合模型表明，遗传因素控制了对应激性生活事件诱发抑郁效应的敏感性。在遗传风险最低的个体（同卵双胞胎，双胞胎未受影响）中，未暴露于严重事件和暴露于严重事件的个体每月发生重度抑郁症的概率分别预计为0.5%和6.2%。在遗传风险最高的个体（同卵双胞胎，双胞胎受影响）中，这些概率分别为1.1%和14.6%。线性回归分析表明，在预测重度抑郁症发作时存在显著的基因与环境相互作用。
遗传因素部分通过改变个体对应激性生活事件诱发抑郁效应的敏感性来影响重度抑郁症的发作风险。
