A mechanism of sleep disturbance in bipolar disorder

描述（由申请人提供）：双相情感障碍是一种严重的、高复发性的疾病，是全球十大致残原因之一。尽管双相情感障碍的治疗取得了显著进展，但研究一致表明，复发率高得惊人，甚至在接受并坚持治疗的患者中也是如此。此外，双相患者在疾病发作之间仍然有症状。这些高复发率和持续的功能障碍表明存在一个潜在的过程，或多个过程，使双相情感障碍患者容易出现新的疾病发作。一项重要的公共卫生优先事项是确定这些过程——这一目标对改善预防和治疗干预结果具有深远影响。几条研究路线汇聚在一起，强调睡眠障碍是抑郁和躁狂症状发病的关键过程，因此在双相情感障碍患者中维持。然而，到目前为止，普遍的睡眠不足是双相情感障碍的特征，很少得到实证的关注。因此，本研究的目的是研究双相情感障碍患者睡眠受到干扰的潜在机制。该研究项目首次提供了对社会授时子理论提出的核心因果机制的直接实证评估，即双相情感障碍患者的睡眠障碍是由社会节律中断引起的，而社会节律中断可由压力生活事件触发（Ehlers等人，1988；Frank等人，2000）。具体来说，该研究计划的目的是在精心筛选的优生双相门诊患者和匹配的健康对照中，检查睡眠是否会在经历扰乱社会节奏的压力事件后受到干扰。生活事件的发生和影响、社会节律的稳定性和睡眠质量将在8周的时间内进行前瞻性测量，使用(1)每日日记评估压力事件和社会节律的稳定性，(2)连续佩戴的活动记录仪评估睡眠-觉醒周期和睡眠质量。将进行半结构化的生活压力访谈，以评估日常评估期间报告的事件的主观和客观影响。这种方法将使我们能够开始描绘一个潜在的关键机制，通过该机制，双相情感障碍患者的睡眠可能会受到干扰。本研究的长期目标是利用所获得的知识促进转化研究，以开发针对双相情感障碍患者的新的治疗和新的预防策略。

DESCRIPTION (provided by applicant): Bipolar disorder is a severe and highly recurrent disorder that is ranked among the top 10 causes of disability worldwide. Despite remarkable advances in the treatment of bipolar disorder, studies consistently document alarmingly high rates of relapse, even among patients who receive, and adhere to, treatment. Additionally, bipolar patients continue to be symptomatic between episodes of illness. These high rates of relapse and continued dysfunction suggest the presence of an underlying process, or multiple processes, that render individuals with bipolar disorder vulnerable to the onset of new episodes of illness. An important public health priority is to identify these processes - a goal with profound implications for improving prevention and treatment intervention outcomes. Several lines of research converge to highlight sleep disturbance as a process of key importance in the onset of both depressive and manic symptoms, and thus in the maintenance of bipolar disorder among patients. To date, however, the pervasively poor sleep that is characteristic of bipolar disorder has received minimal empirical attention. Accordingly, the aim of the proposed research is to investigate a potential mechanism by which sleep is disturbed in bipolar disorder. This program of research provides the first direct empirical evaluation of a central causal mechanism posited by social zeitgeber theory, namely, that sleep disturbance in bipolar disorder is caused by disruptions in social rhythms, which can be triggered by stressful life events (Ehlers et al., 1988; Frank et al., 2000). Specifically, the aim of the proposed program of research is to examine whether sleep is disturbed following the experience of stressful events that disrupt social rhythms, in a sample of carefully screened euthymic bipolar outpatients and matched healthy controls. The occurrence and impact of life events, stability of social rhythms, and quality of sleep, will be measured prospectively over the course of an 8 week period using (1) a daily diary for the assessment of stressful events and stability of social rhythms, and (2) a continuously worn actigraph for the daily assessment of sleep-wake cycles and sleep quality. Semi-structured life stress interviews will be administered to assess subjective and objective impact of the events reported during the daily assessment period. This methodology will allow us to begin to delineate a potentially critical mechanism by which sleep may be disturbed in bipolar patients. The long-term goal of this research is to use the knowledge gained to facilitate translational research with the aim of developing new treatment and new prevention strategies that target sleep disturbance among bipolar patients.