Genetic and Behavioral Predictors of Susceptibility to Social Stress

智力优势：长期社会压力与不良健康结果（包括较高的死亡率）之间的密切关系已得到充分证实。然而，这种关系产生的机制，以及个体对社会压力的反应变化的预测因素，仍然知之甚少。由于需要整合工具、分析方法和跨越多个学科的观点，包括动物行为学、心理学、社会学、遗传学和基因组学，这一主题的研究变得复杂。本项目的研究借鉴了这些领域的工具和理论，探讨了介导对社会压力反应的两种潜在机制：行为策略-特别是建立密切的社会关系；以及基因变异，这可能会改变个体对这些影响的易感性。为了做到这一点，它利用了一个强大的动物模型来衡量社会压力，即圈养的雌性恒河猴的统治地位。具体来说，它测试了社会关系、遗传变异以及两者的结合如何通过全基因组基因表达来改变对社会压力的生物反应。因此，该项目扩展了先前的论证，即显性等级诱导的压力对基因调控有强有力的影响。这项工作的意义有三方面。首先，它揭示了行为策略和基因型的个体差异如何减轻或加剧慢性应激的有害影响。其次，它确定了哪些生理过程被行为策略和遗传变异所改变。最后，它提供了一个宝贵的机会来训练PI（研究员）在新的领域，包括心理学，遗传学和基因组学，这对他作为一个独立的跨学科研究人员的发展非常重要。更广泛的影响：这个提议的更广泛的影响有三个方面：1)它不仅通过对研究员的指导，而且通过让他参与杜克大学本科生的培训，促进了教学、培训和学习。具体来说，研究员培训两名本科生进行数据收集、分析、综合和展示，最终目标是让本科生在杜克大学本科生研究海报研讨会上展示他们的发现。2)通过PI在达勒姆和教堂山当地的K-12学校以及自然研究中心（北卡罗来纳自然科学博物馆的一部分）的公众听众中介绍动物行为、进化以及社会和行为研究，促进公众对科学研究的兴趣和理解。3)最后，它通过增进对不利的社会环境（其中许多与低社会经济地位有关）如何助长健康和福祉差距的理解，对整个社会作出贡献。这些发现对于确定人口中最易受影响的成员和建立有效的干预措施以减轻社会压力的不利影响至关重要。

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.