Sleep reactivity as a novel mechanism in Shift Work Disorder

睡眠反应性是轮班工作障碍的一种新机制

• 批准号: 10530756
• 负责人: Philip Cheng
• 金额: $ 76万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10530756
• 关键词: Accidents; Acute; Address; Affect; Automobile Driving; Biological Clocks; Circadian Rhythms; Circadian desynchrony; Clinical; Cognitive Therapy; Data; Disease; Disease remission; Drowsiness; Education; Future; Goals; Light; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Noise; Pharmaceutical Preparations; Precision therapeutics; Public Health; Randomized Controlled Trials; Reporting; Research; Residual state; Risk; Role; Safety; Sampling; Schedule; Severities; Shift-Work Sleep Disorder; Sleep; Sleep Deprivation; Sleep disturbances; Sleeplessness; Stimulant; Stimulus; Symptoms; Testing; Work; alertness; circadian; clinical translation; first responder; hospital services; hypnotic; novel; occupational stress; operation; persistent symptom; precision medicine; prospective; reduce symptoms; shift work; stressor; symptom management; trait

Project Summary/Abstract All essential 24-hr operations (e.g., first responders, hospital services) rely on nightshift workers who forgo nocturnal sleep for work. Shift workers comprise 20% of the workforce, with 15 million regularly working nights. Most do not adapt to the inverted sleep-wake schedule, resulting in shift work disorder (SWD) characterized by excessive sleepiness and/or insomnia with sleep loss. Furthermore, because nightshifts are critical to safety- sensitive operations, the risk for catastrophic accidents makes SWD a threat to public health and safety. There remain critical gaps in the clinical translation of shift work research into validated treatments for SWD. One gap is a lack of mechanistic research in large clinical samples of SWD that probe pertinent treatment targets. As such, treatments have predominantly focused on symptom management (e.g., stimulants to maintain alertness and hypnotic medications for sleep). Symptom management alone leaves the underlying mechanisms unabated which can continue to cause a myriad of acute and long-term problems and morbidities. To address this gap, the overall objective of this proposal is to elucidate critical and novel mechanisms driving SWD. Our long-term goal is to develop a treatment that identifies and targets the appropriate underlying mechanisms in SWD. Our pilot data indicates that in addition to circadian misalignment (i.e., a mismatch between the body- clock and the sleep-work schedule), one novel and critical mechanism in SWD is sleep reactivity. Sleep reactivity is a trait where sleep is easily disrupted by environmental stimuli and stressors. Our pilot data in a cross-sectional sample suggests that sleep reactivity predicts persistent SWD symptoms even after reducing circadian misalignment. We also show that sleep reactivity can be reduced with Cognitive Behavioral Therapy (CBT). However, sleep reactivity has not been experimentally disassociated from circadian misalignment as an independent causal mechanism of SWD. This research is critical because it would demonstrate that SWD treatment should target sleep reactivity independently from circadian misalignment. To do this, we propose a two-step mechanistic randomized controlled trial in SWD stratified by high and low sleep reactivity (N=150): the first step probes circadian misalignment using timed bright light exposure, and the second step reduces sleep reactivity with Cognitive Behavioral Therapy. Our central hypothesis is that symptoms of SWD will reduce proportionately with circadian realignment in SWD with low sleep reactivity; however, both insomnia (Aim 1) and sleepiness (Aim 2) symptoms will persist in SWD with high sleep reactivity even after experimental reduction of circadian misalignment. In those with persistent symptoms despite reduced circadian misalignment, further reducing sleep reactivity with CBT would result in reductions in symptoms (Aims 3 & 4). Upon completion, results from this study will have established sleep reactivity as a novel causal mechanism of SWD to be inform future precision medicine approaches for this highly prevalent and undertreated disorder.

项目概要/摘要 所有必要的 24 小时运营（例如急救人员、医院服务）都依赖于夜班工作人员，他们放弃了 晚上睡觉是为了工作。轮班工人占劳动力的 20%，有 1,500 万人在夜间正常工作。 大多数人不适应倒置的睡眠-觉醒时间表，导致轮班工作障碍（SWD），其特征是 过度嗜睡和/或失眠伴睡眠不足。此外，由于夜班对于安全至关重要 敏感作业、灾难性事故的风险使社会福利署对公众健康和安全构成威胁。那里 在将轮班工作研究临床转化为有效的 SWD 治疗方法方面仍然存在重大差距。一处间隙 缺乏对SWD的大型临床样本进行机制研究来探究相关的治疗目标。作为 因此，治疗主要集中在症状管理（例如，使用兴奋剂来保持警觉） 和用于睡眠的催眠药物）。症状管理本身就留下了潜在的机制 有增无减，这可能继续导致无数急性和长期的问题和发病率。致地址 鉴于这一差距，本提案的总体目标是阐明推动社会福利署的关键和新颖机制。我们的 长期目标是开发一种治疗方法，识别并针对适当的潜在机制 社署。我们的试点数据表明，除了昼夜节律失调（即身体之间的不匹配） 时钟和睡眠工作时间表），SWD 的一种新颖且关键的机制是睡眠反应性。睡觉 反应性是一种睡眠很容易受到环境刺激和压力源干扰的特征。我们的试点数据 横截面样本表明，即使在减少睡眠反应性后，睡眠反应性仍可预测持续的 SWD 症状 昼夜节律失调。我们还表明，认知行为疗法可以减少睡眠反应性 （认知行为治疗）。然而，睡眠反应性尚未在实验中与昼夜节律失调作为一种影响因素分开。 社会福利署的独立因果机制。这项研究至关重要，因为它将证明社署 治疗应针对睡眠反应性，独立于昼夜节律失调。为此，我们建议 SWD 的两步机制随机对照试验按高低睡眠反应性分层（N = 150）： 第一步使用定时强光照射来探测昼夜节律失调，第二步减少睡眠 认知行为疗法的反应。我们的中心假设是 SWD 的症状会减少 与睡眠反应性低的 SWD 的昼夜节律调整成比例；然而，两者都失眠（目标1） 即使在实验结束后，睡眠反应性较高的 SWD 中嗜睡（目标 2）症状仍将持续存在 减少昼夜节律失调。对于那些尽管昼夜节律减少但症状持续存在的人 错位，通过 CBT 进一步减少睡眠反应将导致症状减轻（目标 3 和 4）。 完成后，这项研究的结果将确立睡眠反应性作为一种新的因果机制 社会福利署将为未来针对这种高度流行且治疗不足的疾病的精准医疗方法提供信息。