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

• 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
• 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' 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

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）：重度抑郁障碍/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证明。抑郁症与较高的肥胖率、代谢综合征（MetSyn）和糖尿病以及更大的胰岛素抵抗（代谢失调的指标和已知的心血管疾病风险因素）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。炎症可能起着关键作用。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，抑郁症与几种炎症标志物有关。文献中缺少对抑郁症与脂肪细胞因子之间关系的系统研究，脂肪细胞释放的分泌蛋白在炎症过程中起关键作用，并被认为在动脉粥样硬化和代谢失调中非常重要。在这个应用中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，以及瘦素，一种促炎脂肪细胞因子，密切参与代谢、能量平衡和自主神经系统功能的调节。脂联素和瘦素都与未来心血管事件和亚临床心血管疾病的风险增加独立相关。我们将使用来自全国妇女健康研究（SWAN）的现有的、特征良好的非裔美国妇女和高加索妇女队列进行我们的研究，其中包括一项观察队列研究（N=581）和一项回顾性队列研究（N=266），无心血管疾病史。糖尿病或MetSyn)，研究5年来抑郁和当前抑郁症状终生史与脂联素和瘦素的横断面和纵向关系以及这些脂肪细胞因子的变化。支持从nia现有的SWAN库中存储的血清标本中检测脂联素和瘦素，并对我们的发现进行分析和传播。通过使用现有的，具有良好特征的血清标本的队列，我们有一个独特的机会，以一种高度经济有效的方式来测试我们提出的新假设。我们相信这项研究将为未来的R01工作提供重要的数据，这将扩展首席研究员的研究计划，更广泛地研究慢性压力、情绪和代谢失调之间的相互关系。研究结果有可能对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。公共卫生相关性：这项拟议的研究将检查抑郁症是否与脂肪细胞因子、脂联素和瘦素有关，脂肪组织分泌的生物活性分子在动脉粥样硬化和代谢失调中起关键作用，在中年黑人和白人妇女的样本中。这项研究的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。