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.

R03AG045301

2013-09-15

2016-08-31