Sleep: A Novel Pathway Linking Major Depression and Cardiovascular Disease

睡眠：连接重度抑郁症和心血管疾病的新途径

• 批准号: 8136117
• 负责人: Martica Helon Hall
• 金额: $ 69.67万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8136117
• 关键词: Accounting; Acute; Address; Adult; Affect; Age; Atherosclerosis; Attenuated; Biological; Blood Glucose; Blood Pressure; Cardiac; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Clinical; Comorbidity; Confounding Factors (Epidemiology); Coupled; Data; Depressed mood; Development; Diet; Disease; Disease remission; Dyslipidemias; Equation; Evidence based intervention; Exhibits; Frequencies; Functional disorder; Future; Gender; Health behavior; Individual; Intervention; Laboratories; Link; Major Depressive Disorder; Measures; Mediating; Mediator of activation protein; Mental Depression; Metabolic syndrome; Modeling; Morbidity - disease rate; Obesity; Outcome; Participant; Pathway interactions; Pharmaceutical Preparations; Physical activity; Physiologic pulse; Polysomnography; Population; Race; Recording of previous events; Recurrence; Research; Risk; Risk Factors; Role; Scientific Advances and Accomplishments; Severities; Sleep; Sleep Apnea Syndromes; Sleep disturbances; Smoking; Social isolation; Socioeconomic Status; Statistical Models; Stress; Symptoms; Testing; Therapeutic; Thick; Time; Woman; biobehavior; cardiovascular disorder risk; cardiovascular risk factor; cohort; design; digital; disorder risk; effective intervention; evidence base; experience; follow-up; heart rate variability; high risk; improved; indexing; insight; interest; intima media; member; men; mortality; novel; pre-clinical; prevent; prospective; psychosocial; public health relevance; recurrent depression; research study; sex; therapeutic target; tonometry

DESCRIPTION (provided by applicant): Major depression ranks among the leading biobehavioral risk factors for cardiovascular (CV) morbidity and mortality. Research has revealed several pathways through which depression increases CV risk including health behaviors and psychosocial functioning. That depression remains a significant predictor of CV disease (CVD) after intervening to improve health behaviors and psychosocial functioning in adults with depression suggests that additional, important risk factors have yet to be identified. We have developed a conceptual model that extends previous research on depression and CV risk by considering sleep as a novel biobehavioral mediator through which depression increases CV risk. We hypothesize that sleep disturbance, including decreased sleep duration, continuity and depth and increased sleep disordered breathing contribute to the increased CV risk observed in adults with major depression. Importantly, each of these components of sleep is modifiable and may represent promising therapeutic targets for reducing the cardiovascular consequences of major depression. The proposed 5-year study will evaluate these relationships in a well-characterized cohort of 200 adults with a history of recurrent major depressive disorder (MDD) who underwent psychiatric assessments and sleep studies in our laboratory approximately 10 to 30 years ago (T1). Participants, who were medically healthy without clinical cardiovascular disease at T1, exhibited profound sleep disturbances that persisted during remission. Members of this cohort have expressed great interest in the proposed follow-up study (T2). Proposed T2 measures include follow-up psychiatric assessments and sleep studies coupled with assessment of CV risk and subclinical disease including indices of autonomic imbalance, endothelial dysfunction, preclinical atherosclerosis and the metabolic syndrome. We will also assess health behaviors, psychosocial functioning and potential confounding variables. Together, these data will provide the first test of the hypothesized paths in our conceptual model. Our primary aim is to use T1 depression and sleep data in conjunction with T2-assessed CV outcomes to evaluate whether PSG-assessed sleep disturbance attenuates the prospective relationship between depression and CV risk and subclinical disease. Our secondary aim is to evaluate both wake and sleep "pathways" in the same model, using data collected at T2, including objective assessment of physical activity. The use of multiple-group structural equation models will provide the opportunity to evaluate whether relationships among depression, sleep disturbance and CV risk/subclinical disease differ by age and gender (exploratory aim). In future studies, experimental approaches will be needed to establish sleep as a causal pathway, identify the biological mechanisms through which specific components of disturbed sleep in depressed individuals increase CV risk, and develop evidence-based sleep interventions to prevent or attenuate the cardiovascular consequences of major depression. PUBLIC HEALTH RELEVANCE: The proposed study will be the first to evaluate sleep as a novel pathway through which depression increases cardiovascular disease risk, morbidity and mortality. Insights into the role of sleep disturbance in the link between major depression and cardiovascular disease is essential to our understanding of the pathophysiology of this prevalent and costly disease. Because sleep represents a modifiable pathway through which depression increases cardiovascular disease risk, it holds promise for the design and implementation of effective, evidence-based interventions to prevent and/or treat the cardiovascular consequences of major depression.

描述（由申请人提供）：重度抑郁症是心血管（CV）发病率和死亡率的主要生物行为风险因素之一。研究揭示了抑郁症增加CV风险的几种途径，包括健康行为和心理社会功能。在干预改善抑郁症成人的健康行为和心理社会功能后，抑郁症仍然是CV疾病（CVD）的重要预测因素，这表明其他重要的风险因素尚未确定。我们开发了一个概念模型，通过将睡眠视为一种新的生物行为介质，通过这种介质，抑郁症会增加CV风险，从而扩展了先前关于抑郁症和CV风险的研究。我们假设睡眠障碍，包括睡眠持续时间，连续性和深度减少以及睡眠呼吸障碍增加，导致成年抑郁症患者CV风险增加。重要的是，睡眠的这些组成部分中的每一个都是可以改变的，并且可能代表了减少重性抑郁症的心血管后果的有希望的治疗靶点。这项为期5年的研究将在一个由200名有复发性重度抑郁症（MDD）病史的成年人组成的具有良好特征的队列中评估这些关系，这些成年人大约在10至30年前（T1）在我们的实验室接受了精神病学评估和睡眠研究。参与者在T1时医学上健康，没有临床心血管疾病，在缓解期间表现出严重的睡眠障碍。该队列的成员对拟定的随访研究（T2）表示了极大的兴趣。拟定的T2指标包括随访精神病学评估和睡眠研究，以及CV风险和亚临床疾病评估，包括自主神经失衡、内皮功能障碍、临床前动脉粥样硬化和代谢综合征指数。我们还将评估健康行为，心理社会功能和潜在的混杂变量。总之，这些数据将为我们的概念模型中的假设路径提供第一次测试。我们的主要目的是使用T1抑郁和睡眠数据结合T2评估的CV结局来评估PSG评估的睡眠障碍是否减弱抑郁与CV风险和亚临床疾病之间的前瞻性关系。我们的第二个目标是在同一个模型中评估清醒和睡眠“通路”，使用在T2收集的数据，包括身体活动的客观评估。使用多组结构方程模型将提供机会，以评估抑郁、睡眠障碍和CV风险/亚临床疾病之间的关系是否因年龄和性别而异（探索性目的）。在未来的研究中，将需要实验方法来建立睡眠作为因果途径，确定抑郁症患者睡眠障碍的特定成分增加CV风险的生物学机制，并开发基于证据的睡眠干预措施以预防或减轻重度抑郁症的心血管后果。 公共卫生相关性：这项拟议的研究将是第一个评估睡眠作为一种新的途径，通过这种途径抑郁症增加心血管疾病的风险，发病率和死亡率。深入了解睡眠障碍在重性抑郁症和心血管疾病之间的联系中的作用，对于我们理解这种流行且昂贵的疾病的病理生理学至关重要。由于睡眠代表了抑郁症增加心血管疾病风险的可改变途径，因此它有望设计和实施有效的循证干预措施，以预防和/或治疗重度抑郁症的心血管后果。