The Impact of Stress and Psychosocial Factors on Inflammation in Women

描述（由申请人提供）：本提案是对题为“老龄化社会和行为数据集的二次分析（R03）”的PA-10-139的回应。我们的研究计划的长期目标是检查慢性应激和心理社会因素对代谢失调和心血管疾病（CVD）风险的影响，并调查这些关联背后的生物学机制。PI有一项积极的研究（1R21HL091290），使用NIA/ ninr资助的全国妇女健康研究（SWAN）和辅助的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。拟议的研究将通过扩大我们可用的社会心理测量的广度，大大加强这项工作。我们建议利用额外的现有SWAN数据来测量慢性压力（财务压力、感知压力、压力生活事件、感知歧视）和社会心理功能（敌意、焦虑、乐观、社会支持），以及来自PI活跃R21的脂联素和瘦素数据。在581名SWAN参与者（225名黑人女性，356名白人女性）中，研究压力/社会心理因素与这些关键肥胖相关炎症标志物之间的横断面和5年纵向关联。目的是：1)确定慢性应激是否与脂联素和瘦素水平的基线和5年变化有关；2)确定社会心理因素是否与脂联素和瘦素水平的基线和5年变化有关。次要目的是研究压力和心理社会功能（包括抑郁）的测量途径，以及这些与肥胖相关的炎症标志物，并调查假设关联中潜在的种族差异。该项目将提供重要的数据，将促进一个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。通过添加已经进行的研究（R21HL091290）并利用现有SWAN数据的丰富性，拟议的研究将允许更全面地表征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应激和社会心理因素可能导致女性代谢失调和心血管疾病风险的关键炎症途径的理解。此外，该研究解决了肥胖和心血管疾病等关键的公共卫生问题，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. PUBLIC HEALTH RELEVANCE: The proposed study has high public health relevance as it will yield important information about pathways by which stress and psychosocial factors may lead to obesity, diabetes and heart disease in women. These diseases are leading causes of death and disability in the US and worldwide. Knowledge gained likely will contribute to future treatment and prevention efforts for these critical public health problems.