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

描述(申请人提供)：抑郁症是最普遍和最衰弱的精神疾病之一。在老年人中，抑郁是最常见的情感痛苦原因，晚年抑郁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，在预测抑郁症的发病、严重程度和病程时，遗传特征与环境影响相互作用。人们对评估这种基因与环境的相互作用有相当大的兴趣，包括考察潜在遗传影响的孪生研究和评估特定基因潜在调节作用的候选基因研究。在这项拟议的研究中，我们试图通过对大量基于人群的老年人样本(即健康和退休研究)的现有数据进行重新分析，以建立在先前的基因与环境研究的基础上，提供一种新的抑郁症基因与环境模型的测试，该模型整合了遗传和社会视角。具体地说，建议的研究试图通过以下方式建立在先前的基因-环境研究的基础上：(A)通过使用基因-环境范围交互研究(GEWIS)方法来扩展对遗传影响的评估，(B)将环境影响的评估集中于一直与抑郁相关的压力源(即，社会压力)，(C)分解对社会压力的评估，以评估某些关系(例如，一个人与配偶或伴侣的关系)中的压力是否比其他关系中的压力(例如，一个人与孩子、亲戚和朋友的关系)，以及(D)评估易感性和差异易感基因 按环境模型。目前还没有发表的关于抑郁症的GEWIS研究，因此拟议的研究将是一个重要的科学进步，因为它将是第一批使用这种方法来检验抑郁症对环境影响的遗传脆弱性的研究之一。此外，很少有研究评估抑郁症的差异易感性模型，特别是在老年人中，因此这项研究将是第一批比较老年人抑郁症易感性和不同环境易感性模型的研究之一。最后，通过考察几种社会关系类型的社会压力，拟议的研究结果将在确定压力最强的特定社会关系方面取得重要进展 与抑郁症相关，可作为预防和治疗高危老年人抑郁症的靶点。

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.