Pathophysiology of Circadian Rhythm Delayed Sleep Wake Phase Disorder

项目摘要/摘要 睡眠-觉醒延迟相障碍(DSWPD)是一种影响数百万美国人的昼夜节律紊乱 从而导致不利的健康和性能后果。DSWPD患者经常睡眠不足 在工作/学校周期间，由于在社交要求的时间入睡和醒来有困难，以及 患者出现过度嗜睡，严重干扰了白天的功能。现行做法 参数指南和荟萃分析考虑了DSWPD的现有治疗策略，包括晨光 暴露、晚间外源性褪黑素和计时疗法无效/“虚弱”可能是由于有限 了解DWSPD的病理生理学和依从性。这项建议的总体目标是改善我们的 了解DSWPD的病理生理学，将有助于开发新的基于昼夜节律的治疗方法 改善DSWPD患者健康、工作表现和幸福感的策略。我们将进行 在两个实验室内昼夜节律方案之前进行动态和基线昼夜节律评估，以解决我们的 目的：1)一个恒定的常规方案，以准确评估昼夜节律的幅度和相位的中央和 外周昼夜节律，以及2)检查认知和生理的夜间光线暴露方案 回应。我们还将确定是否可以准确地预测DSWPD患者的昼夜节律 一种新的昼夜节律生物标志物。我们的基础人体昼夜节律和临床试验研究的初步数据 为这项提议做好准备。我们的总体目标和宗旨是支持NIH精密医学倡议，即2021年 国家健康研究院睡眠研究计划和NHLBI战略愿景计划。

PROJECT SUMMARY/ABSTRACT Delayed sleep-wake phase disorder (DSWPD) is a circadian rhythm disorder that impacts millions of Americans resulting in adverse health and performance consequences. Patients with DSWPD often obtain insufficient sleep during the work/school week due to difficulties falling asleep and awakening at socially required times, and patients present with excessive sleepiness that significantly interferes with daytime function. Current practice parameter guidelines and metanalyses consider existing treatment strategies for DSWPD, include morning light exposure, evening exogenous melatonin and chronotherapy to be ineffective/“weak” perhaps due to limited understanding of DWSPD pathophysiology and compliance. The overall goal of this proposal is to improve our understanding of DSWPD pathophysiology, which will inform development of new circadian based treatment strategies to improve the health, performance, and well-being of patients with DSWPD. We will conduct ambulatory and baseline circadian phase assessments prior to two in-lab circadian protocols to address our aims: 1) a constant routine protocol to precisely assess the circadian amplitude and phase of central and peripheral circadian rhythms, and 2) a nighttime light exposure protocol to examine cognitive and physiological responses. We will also determine if circadian phase can be accurately predicted in patients with DSWPD using a novel biomarker of circadian phase. Preliminary data from our basic human circadian and clinical trial research set the stage for this proposal. Our overall goal and aims support the NIH Precision Medicine Initiative, the 2021 National Institutes of Health Sleep Research Plan, and the NHLBI Strategic Vision plan.