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

基本信息

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
项目类别：
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

项目摘要

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）：主要抑郁症是心血管（CV）发病率和死亡率领先的生物行为风险因素。研究揭示了几种途径，抑郁症会增加简历风险，包括健康行为和社会心理功能。干预以改善抑郁症的成年人的健康行为和社会心理功能后，抑郁症仍然是CV疾病（CVD）的重要预测指标，这表明尚未确定其他重要的风险因素。我们已经开发了一种概念模型，该模型通过将睡眠视为一种新型的生物行为介体来扩展对抑郁症和简历风险的研究，通过该研究会增加CV风险。我们假设睡眠障碍，包括睡眠持续时间减少，连续性和深度以及睡眠不足的呼吸增加有助于大抑郁症的成年人观察到的CV风险增加。重要的是，睡眠的每个组成部分都是可修改的，可能代表了减少严重抑郁症的心血管后果的有希望的治疗靶标。拟议的5年研究将评估200名有重大抑郁症病史（MDD）的200名成年人的良好表征人群中的这些关系，他们大约在10至30年前在我们的实验室中接受了精神病评估和睡眠研究（T1）。在T1处没有临床心血管疾病的没有临床心血管疾病的医学健康的参与者表现出严重的睡眠障碍，在缓解过程中持续存在。该队列的成员对拟议的后续研究表达了极大的兴趣（T2）。拟议的T2措施包括随访的精神病评估和睡眠研究，再加上简历风险和亚临床疾病的评估，包括自主性失衡，内皮功能障碍，临床前动脉粥样硬化和代谢综合征的指标。我们还将评估健康行为，社会心理功能和潜在的混杂变量。总之，这些数据将在我们的概念模型中对假设的路径进行首次测试。我们的主要目的是将T1抑郁症和睡眠数据与T2评估的CV结果结合使用，以评估PSG评估的睡眠障碍是否会减轻抑郁症与CV风险与亚临床疾病之间的前瞻性关系。我们的次要目的是使用T2收集的数据，包括对体育活动的客观评估，评估同一模型中的唤醒和睡眠“途径”。多组结构方程模型的使用将为评估抑郁症，睡眠障碍和简历风险/亚临床疾病之间的关系是否因年龄和性别而有所不同（探索目的）。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，确定抑郁症患者中干扰睡眠的特定组成部分的生物学机制增加了CV风险，并制定了基于证据的睡眠干预措施，以防止或减轻重大抑郁症的心血管后果。公共卫生相关性：拟议的研究将是第一个评估睡眠作为一种新的途径，抑郁症会增加心血管疾病风险，发病率和死亡率。对睡眠障碍在严重抑郁症和心血管疾病之间联系中的作用的见解对于我们对这种普遍且昂贵的疾病的病理生理学的理解至关重要。由于睡眠代表了一种可修改的途径，抑郁症会增加心血管疾病风险，因此它有望设计和实施有效的，基于证据的干预措施，以预防和/或治疗严重抑郁症的心血管后果。