The Impact of Stress and Psychosocial Factors on Inflammation in Women

描述（由申请人提供）：本提案是对PA-10-139的响应，标题为“老龄化中社会和行为数据集的二次分析（R 03）"。我们研究计划的长期目标是研究慢性压力和心理社会因素对代谢失调和心血管疾病（CVD）风险的影响，并研究这些关联背后的生物学机制。PI有一项积极的研究（1 R21 HL 091290），使用来自NIA/NINR资助的全国妇女健康研究（SWAN）和辅助SWAN心理健康研究的数据，调查抑郁症对脂联素和瘦素的影响。脂联素是脂肪细胞分泌的最丰富的抗炎脂肪细胞因子，瘦素是一种促炎脂肪细胞因子，与代谢调节、能量平衡和自主神经系统功能密切相关。拟议的研究将大大加强这项工作，扩大我们可以利用的心理社会措施的广度。我们建议利用更多现有的SWAN数据对慢性压力进行多项测量（财务紧张、感觉到的压力、压力性生活事件、感觉到的歧视）和社会心理功能（敌意，焦虑，乐观，社会支持），连同来自PI的活性R21的脂联素和瘦素数据，在581名SWAN参与者中检查压力/心理社会因素与这些关键的肥胖相关炎症标志物之间的横向和5年纵向关联（225名黑人妇女，356名白色妇女）。目标是：1）确定慢性压力是否与脂联素和瘦素水平的基线和5年变化相关; 2）确定心理社会因素是否与脂联素和瘦素水平的基线和5年变化相关。次要目的是检查压力和心理社会功能（包括抑郁症）以及这些肥胖相关炎症标志物的测量方法之间的途径，并调查假设关联中的潜在种族差异。该项目将提供关键数据，促进更全面和综合的生物心理社会框架的发展，以指导未来的研究和实现我们的研究计划的目标。通过添加到一项正在进行的研究（R21 HL 091290）中并利用现有SWAN数据的丰富性，拟议的研究将允许更全面地描述可能与女性重要脂肪因子生物标志物相关的心理和社会过程。因此，这项工作有可能极大地扩展我们对一个关键炎症途径的理解，压力和心理社会因素可能会导致女性代谢失调和CVD风险。此外，该研究解决了肥胖和心血管疾病的关键公共卫生问题，因此具有高度的公共卫生相关性。

DESCRIPTION (provided by applicant): This proposal is responsive to PA-10-139 entitled, "Secondary Analyses of Social and Behavioral Datasets in Aging (R03)". The long-term goals of our research program are to examine the impact of chronic stress and psychosocial factors on metabolic dysregulation and cardiovascular disease (CVD) risk and to investigate the biologic mechanisms underlying these associations. The PI has an active study (1R21HL091290) using data from the NIA/NINR-funded Study of Women's Health across the Nation (SWAN), and the ancillary SWAN Mental Health Study, to investigate the impact of depression on adiponectin and leptin. Adiponectin is the most abundant anti-inflammatory adipocytokine secreted by adipocytes and leptin is a pro-inflammatory adipocytokine intimately involved in metabolic regulation, energy balance, and autonomic nervous system functioning. The proposed study will significantly enhance this work by expanding the breadth of psychosocial measures available to us. We propose to utilize additional existing SWAN data on multiple measures of chronic stress (financial strain, perceived stress, stressful life events, perceived discrimination) and psychosocial functioning (hostility, anxiety, optimism, social support), together with the adiponectin and leptin data from the PI's active R21, to examine both cross-sectional and 5-year longitudinal associations between stress/psychosocial factors and these critical obesity-related inflammatory markers in 581 SWAN participants (225 black women, 356 white women). Aims are: 1) to determine if chronic stress is associated with baseline and 5-year changes in adiponectin and leptin levels; and 2) to determine if psychosocial factors are associated with baseline and 5-year changes in adiponectin and leptin levels. Secondary aims are to examine pathways among the measures of stress and psychosocial functioning, including depression, and these obesity-related inflammatory markers, and to investigate potential race differences in the hypothesized associations. The project will provide crucial data that will foster development of a more comprehensive and integrative biopsychosocial framework to guide future studies and achieve the goals of our research program. By adding to a study already in progress (R21HL091290) and utilizing the richness of the existing SWAN data, the proposed study will allow a fuller characterization of psychological and social processes that may relate to important adipokine biomarkers in women. Thus, this work has the potential to greatly expand our understanding of a critical inflammatory pathway by which stress and psychosocial factors may contribute to metabolic dysregulation and CVD risk in women. Moreover, the study addresses the critical public health problems of obesity and cardiovascular disease and thus has high public health relevance.