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: 7821256
• 负责人: SUSAN A EVERSON-ROSE
• 金额: $ 18.86万
• 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 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7821256
• 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; 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 Depression; 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; 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）：已记录了重度抑郁症/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。抑郁症与肥胖、代谢综合征（MetSyn）和糖尿病的发病率较高以及胰岛素抵抗、代谢失调的指标和已知的CVD风险因素有关。抑郁症可能通过代谢失调导致CVD风险，但其发生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。从文献中缺失的是抑郁症和脂肪细胞因子之间的关联的系统性研究，脂肪细胞因子是从脂肪细胞释放的分泌蛋白，其在炎症过程中起关键作用，并且被确定为在动脉粥样硬化形成和代谢失调中高度重要。在本申请中特别感兴趣的是脂联素，一种具有胰岛素增敏、抗血栓形成和抗动脉粥样硬化作用的抗炎脂肪细胞因子，以及瘦素，一种密切参与代谢、能量平衡和自主神经系统功能调节的促炎脂肪细胞因子。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。我们将使用来自全国妇女健康研究（SWAN）的非裔美国人和白人妇女的现有的、特征良好的队列进行我们的拟议研究，其中包括观察性队列研究（N=581）和回顾性队列研究（N=266，无CVD病史，糖尿病或MetSyn），以检查两个交叉-抑郁症终身史和当前抑郁症状与脂联素和瘦素的截面和纵向关联以及这些变化脂肪细胞因子超过5年。寻求支持的测定脂联素和瘦素的血清标本储存在国家免疫局现有的天鹅库和分析和传播我们的研究结果。通过使用现有的、具有良好特征的队列和可用的血清标本，我们有一个独特的机会来测试我们以高度成本效益的方式提出的新假设。我们相信这项研究将为未来R 01计划的工作提供重要数据，这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。这些发现有可能产生关于抑郁症对女性代谢失调和心血管风险影响的重要新见解。 公共卫生关系：这项研究将在中年黑人和白色女性样本中检测抑郁症是否与脂肪细胞因子脂联素和瘦素有关，这些脂肪组织分泌的生物活性分子在动脉粥样硬化形成和代谢失调中起着关键作用。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。