Gene-by-Environment Interactions, Social Stress, and Depression in Older Adults

描述（由申请人提供）：抑郁症是一种最普遍和使人衰弱的精神疾病。在老年人中，抑郁症是最常见的情绪痛苦的原因，而晚年抑郁症的有害影响是有据可查的。理解抑郁症的一个常见理论模型是遗传特征与环境影响相互作用的观点，预测抑郁症的发病、严重程度和病程。人们对评估这种基因与环境的相互作用非常感兴趣，包括研究潜在遗传影响的双胞胎研究和评估特定基因潜在调节作用的候选基因研究。在拟议的研究中，我们试图通过对来自老年人的大型人群样本（即健康与退休研究）的现有数据进行重新分析，以建立先前的基因环境研究，从而为整合遗传和社会观点的抑郁症的新型基因环境模型提供测试。具体而言，拟议的研究旨在通过以下途径(a)利用基因-环境相互作用研究（GEWIS）方法扩大对遗传影响的评估，(b)将环境影响的评估集中在一直与抑郁症相关的压力源上（即社会压力），(c)分解对社会压力的评估，以评估某些关系中的压力(例如，一个人与配偶或伴侣的关系)比其他关系（例如，一个人与孩子、亲戚和朋友的关系）中的压力与抑郁的关系更强，并且(d)评估脆弱性和差异易感基因

DESCRIPTION (provided by applicant): Depression is one of the most widespread and debilitating psychiatric disorders. Among older individuals, depression is the most frequent cause of emotional suffering, and the detrimental effects of late-life depression are well documented. One common theoretical model for understanding depression is the perspective that genetic characteristics interact with environmental influences in predicting the onset, severity, and course of depression. There has been considerable interest in evaluating such gene-by-environment interactions, including twin studies that have examined latent genetic influences and candidate gene studies that have evaluated the potential moderating role of specific genes. In the proposed research, we seek to build on prior gene-by-environment research through conducting a reanalysis of existing data from a large, population-based sample of older adults (i.e., the Health and Retirement Study) to provide a test of a novel gene-by-environment model for depression that integrates genetic and social perspectives. Specifically, the proposed research seeks to build on prior gene-by-environment research through (a) expanding the assessment of genetic influences by using a gene-environment-wide interaction study (GEWIS) approach, (b) focusing the assessment of environmental influences on a stressor that has been consistently associated with depression (i.e., social stress), (c) disaggregating the assessment of social stress to evaluate whether stress in certain relationships (e.g., one's relationship with one's spouse or partner) is more strongly associated with depression than is stress in other relationships (e.g., one's relationships with one's childre, relatives, and friends), and (d) evaluating both vulnerability and differential susceptibility gene by-environment models. There are no published GEWIS studies on depression, and so the proposed research will be an important scientific advance as it will be among the first studies to use this methodology in examining the genetic vulnerability to environmental influences on depression. Furthermore, there are few studies that have evaluated the differential susceptibility model with respect to depression, particularly among older individuals, and so the study will be among the first studies to compare vulnerability and differential susceptibility gene-by-environment models of depression in older adults. Finally, by examining social stress across several types of social relationships, the results from the proposed research will provide important advances in identifying particular social relationships for which stress is most strongly associated with depression that can be targeted in preventing and treating depression in at-risk older adults.