Depression, Adipocytokines and Metabolic Dysregulation in Black and White Women

黑人和白人女性的抑郁症、脂肪细胞因子和代谢失调

基本信息

批准号：
7658472
负责人：
SUSAN A EVERSON-ROSE
金额：
$ 23.94万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-01 至 2011-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7658472
关键词：
Adipocytes Adipose tissue Affect African American Age Ancillary Study Anti-Inflammatory Agents Anti-inflammatory Antiatherogenic Area Autonomic nervous system Behavioral Biological Biological Assay Cardiovascular Diseases Cardiovascular system Caucasians Caucasoid Race Chronic stress Classification Clinical Cohort Studies Communities Complex Cross-Sectional Studies Data Development Diabetes Mellitus Disadvantaged Dysthymic Disorder Emotions Epidemiologic Studies Event Freezing Funding Future Goals Inflammation Inflammatory Insulin Insulin Resistance Interview Knowledge Leptin Link Literature Major Depressive Disorder Mediating Menopausal Status Mental Health Metabolic Metabolic Marker Metabolic syndrome Metabolism Minority Groups Morbidity - disease rate Nervous System Physiology Obesity Parents Participant Pathway interactions Pattern Play Predisposition Prevalence Principal Investigator Process Psychosocial Factor Race Recording of previous events Regulation Relative (related person)Reporting Research Risk Risk Factors Role Sampling Serum Socioeconomic Status Specimen Stress Structure Testing Time Urine Woman Women&apos s Health adiponectin atherogenesis base cardiovascular disorder risk cardiovascular risk factor cohort cost depression depressive symptoms diabetes risk energy balance follow up assessment follow-up inflammatory marker insight interest middle age mortality novel programs public health relevance recurrent depression repository secretory protein socioeconomics

项目摘要

DESCRIPTION (provided by applicant): Important links between major depressive disorder/depressive symptoms and risk for cardiovascular disease (CVD) morbidity and mortality have been documented. Depression is associated with higher rates of obesity, metabolic syndrome (MetSyn) and diabetes and greater insulin resistance, indicators of metabolic dysregulation and known CVD risk factors. Depression likely contributes to CVD risk via metabolic dysregulation but precise mechanisms by which this occurs are unknown. Inflammation may play a key role. Atherogenesis, obesity, insulin resistance, diabetes, and MetSyn are known inflammatory processes, and depression has been linked with several inflammatory markers. Missing from the literature is systematic study of the association between depression and adipocytokines, secretory proteins released from adipocytes that play a critical role in the inflammatory process and are identified as highly significant in atherogenesis and metabolic dysregulation. Of specific interest in this application are adiponectin, an anti-inflammatory adipocytokine with insulin-sensitizing, anti-thrombotic and anti-atherogenic effects, and leptin, a pro-inflammatory adipocytokine intimately involved in regulation of metabolism, energy balance, and autonomic nervous system functioning. Both adiponectin and leptin are independently associated with increased risk of future cardiovascular events and increased subclinical cardiovascular disease. We will use an existing, well-characterized cohort of African-American and Caucasian women from the Study of Women's Health Across the Nation (SWAN) for our proposed research, which includes an observation cohort study (N=581) and a retrospective cohort study (N=266 without a history of CVD, diabetes or MetSyn) to examine both cross-sectional and longitudinal associations of lifetime history of depression and current depressive symptoms with adiponectin and leptin and changes in these adipocytokines over 5 years. Support is sought for assays of adiponectin and leptin from serum specimens stored in the NIA-existing SWAN Repository and for analysis and dissemination of our findings. By using an existing, well-characterized cohort with available serum specimens, we have a unique opportunity to test the novel hypotheses we are proposing in a highly cost-efficient manner. We believe this study will provide important data for future R01 efforts planned that will extend the principal investigators' research program to investigate more broadly the interrelationships of chronic stress, emotions and metabolic dysregulation. Findings have the potential to yield significant new insights regarding the impact of depression on metabolic dysregulation and cardiovascular risk in women. PUBLIC HEALTH RELEVANCE: The proposed study will examine whether depression is associated with the adipocytokines, adiponectin and leptin, bioactive molecules secreted by adipose tissue that play a critical role in atherogenesis and metabolic dysregulation, in a sample of middle-aged black and white women. Results of the study will provide significant new information on how depression affects risk for diabetes, metabolic syndrome, obesity and cardiovascular disease in women.

描述（由申请人提供）：重度抑郁症/抑郁症状与心血管疾病 (CVD) 发病率和死亡率风险之间的重要联系已被记录。抑郁症与较高的肥胖、代谢综合征 (MetSyn) 和糖尿病发病率以及较高的胰岛素抵抗、代谢失调指标和已知的 CVD 危险因素有关。抑郁症可能通过代谢失调导致心血管疾病风险，但发生这种情况的确切机制尚不清楚。炎症可能发挥关键作用。动脉粥样硬化、肥胖、胰岛素抵抗、糖尿病和 MetSyn 是已知的炎症过程，抑郁症与多种炎症标志物有关。文献中缺少对抑郁症和脂肪细胞因子之间关系的系统研究，脂肪细胞因子是脂肪细胞释放的分泌蛋白，在炎症过程中发挥着关键作用，并被认为在动脉粥样硬化和代谢失调中非常重要。该应用特别感兴趣的是脂联素（一种具有胰岛素增敏、抗血栓和抗动脉粥样硬化作用的抗炎脂肪细胞因子）和瘦素（一种与代谢、能量平衡和自主神经系统的调节密切相关的促炎脂肪细胞因子）发挥作用。脂联素和瘦素均与未来心血管事件风险增加和亚临床心血管疾病增加独立相关。我们将使用全国妇女健康研究 (SWAN) 中现有的、特征明确的非裔美国人和白人妇女队列来进行我们拟议的研究，其中包括观察队列研究 (N=581) 和回顾性队列研究（N=266，无 CVD、糖尿病或 MetSyn 病史）检查终生抑郁史和当前抑郁症状与脂联素和瘦素及其变化的横断面和纵向关联这些脂肪细胞因子超过 5 年。寻求支持对存储在 NIA 现有 SWAN 存储库中的血清样本进行脂联素和瘦素测定，以及对我们的研究结果进行分析和传播。通过使用现有的、具有良好特征的队列和可用的血清样本，我们有一个独特的机会以高度成本效益的方式测试我们提出的新假设。我们相信这项研究将为未来 R01 计划的工作提供重要数据，这些工作将扩展主要研究人员的研究计划，以更广泛地调查慢性压力、情绪和代谢失调的相互关系。研究结果有可能就抑郁症对女性代谢失调和心血管风险的影响产生重要的新见解。公共健康相关性：拟议的研究将在中年黑人和白人女性样本中检验抑郁症是否与脂肪细胞因子、脂联素和瘦素有关，这些生物活性分子由脂肪组织分泌，在动脉粥样硬化和代谢失调中发挥着关键作用。该研究结果将为抑郁症如何影响女性患糖尿病、代谢综合征、肥胖和心血管疾病的风险提供重要的新信息。