Genetic and Behavioral Predictors of Susceptibility to Social Stress

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Intellectual Merit:A strong relationship between chronic social stress and adverse health outcomes, including higher mortality rates, is well established. However, the mechanisms through which this relationship arises, as well as predictors of variation in individual response to social stressors, remain poorly understood. Research on this topic is complicated by the need to integrate tools, analytical methods, and perspectives that bridge multiple disciplines, including animal behavior, psychology, sociology, and genetics and genomics. The research in this project draws on tools and theories from these fields to investigate two potential mechanisms that mediate the response to social stress: behavioral strategies - particularly the establishment of close social bonds; and genetic variation, which may alter individual susceptibility to these effects. To do so, it utilizes a powerful animal model for social stress, dominance rank in captive female rhesus macaques. Specifically, it tests how social bonds, genetic variation, and the combination of the two modify biological responses to social stress, as measured by genome-wide gene expression. This project therefore expands on previous demonstrations that dominance rank-induced stress has potent effects on gene regulation. The significance of this work is three-fold. First, it reveals how individual variation in behavioral strategies and genotype alleviate or exacerbate the detrimental effects of chronic stress. Second, it identifies what physiological processes are altered by behavioral strategies and genetic variation. Finally, it presents a valuable opportunity to train the PI (Fellow) in new areas, including psychology, genetics, and genomics, that will be important to his development as an independent interdisciplinary researcher.Broader impacts:The broader impacts of this proposal are three-fold: 1) It promotes teaching, training and learning not only through mentorship of the Fellow, but also by including him in the training of undergraduate students at Duke. Specifically, the Fellow trains two undergraduates in data collection, analysis, synthesis and presentation, with the ultimate goal of having the undergraduates present their findings as part of one of Duke's undergraduate research poster symposiums. 2) It promotes public interest and understanding of scientific research through presentations by the PI on animal behavior, evolution, and social and behavioral studies to local K-12 schools in Durham and Chapel Hill, and to a public audience at the Nature Research Center (part of the North Carolina Museum of Natural Sciences). 3) Finally, it contributes to society as a whole by improving the understanding of how adverse social environments, many of which are associated with low socioeconomic status, promote disparities in health and well being. Such findings are critical both to identifying the most susceptible members of the population, and to establishing effective interventions to alleviate the adverse effects of social stress.