The Impact of Stress and Psychosocial Factors on Inflammation in Women

说明(申请人提供)：本提案是对PA-10-139题为“老龄化中社会和行为数据集的二次分析(R03)”的回应。我们研究计划的长期目标是检查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，并调查这些关联的生物机制。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)的数据，以及附属的SWAN心理健康研究，以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，瘦素是一种促炎症脂肪细胞因子，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心理社会措施的广度，大大加强这项工作。我们建议利用更多关于慢性压力(经济压力、感知压力、应激性生活事件、感知歧视)和心理社会功能(敌意、焦虑、乐观、社会支持)的现有SWAN数据，以及PI活动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)中检查压力/心理社会因素与这些关键肥胖相关炎症标记物之间的横断面和5年纵向关系。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；以及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年变化有关。第二个目标是检查压力和心理社会功能(包括抑郁)和这些与肥胖相关的炎症标记物的指标之间的路径，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研究计划的目标。通过增加一项已经在进行的研究(R21HL091290)，并利用现有的丰富的SWAN数据，拟议的研究将允许更全面地描述可能与女性重要的脂肪因子生物标志物有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关键炎症途径的理解，通过该途径，压力和心理社会因素可能导致女性代谢失调和心血管疾病风险。此外，这项研究解决了肥胖和心血管疾病的严重公共卫生问题，因此具有很高的公共卫生相关性。 公共卫生相关性：这项拟议的研究具有很高的公共卫生相关性，因为它将提供有关压力和心理社会因素可能导致女性肥胖、糖尿病和心脏病的途径的重要信息。这些疾病是美国和世界范围内导致死亡和残疾的主要原因。所获得的知识可能有助于今后对这些重大公共卫生问题的治疗和预防工作。

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.