Sleep: A Novel Pathway Linking Major Depression and Cardiovascular Disease

描述（由申请人提供）：重度抑郁症是导致心血管（CV）发病和死亡的主要生物行为危险因素之一。研究揭示了抑郁症增加心血管风险的几种途径，包括健康行为和心理社会功能。在干预改善成人抑郁症患者的健康行为和心理社会功能后，抑郁症仍然是心血管疾病（CVD）的重要预测因子，这表明其他重要的危险因素尚未确定。我们开发了一个概念性模型，通过将睡眠视为一种新的生物行为媒介，抑郁症通过睡眠增加心血管风险，扩展了先前关于抑郁症和心血管风险的研究。我们假设睡眠障碍，包括睡眠持续时间、连续性和深度的减少，以及睡眠呼吸障碍的增加，导致成人重度抑郁症患者心血管风险增加。重要的是，睡眠的每一个组成部分都是可以改变的，可能代表着减少重度抑郁症心血管后果的有希望的治疗目标。这项为期5年的研究将在200名有复发性重度抑郁症（MDD）病史的成年人中对这些关系进行评估，这些成年人大约在10至30年前在我们的实验室接受了精神病学评估和睡眠研究（T1）。在T1时医学上健康且无临床心血管疾病的参与者，在缓解期间表现出持续存在的严重睡眠障碍。该队列的成员对拟议的随访研究（T2）表示了极大的兴趣。建议的T2措施包括随访精神病学评估和睡眠研究，同时评估心血管风险和亚临床疾病，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等指标。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抑郁和睡眠数据以及t2评估的CV结果来评估psg评估的睡眠障碍是否减弱了抑郁和CV风险以及亚临床疾病之间的前瞻性关系。我们的第二个目标是利用T2收集的数据，包括对身体活动的客观评估，在同一模型中评估清醒和睡眠“通路”。多组结构方程模型的使用将提供机会来评估抑郁、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心血管风险的生物学机制，并开发基于证据的睡眠干预措施来预防或减轻重度抑郁症的心血管后果。

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.