Racial Differences in Human Circadian Rhythms

描述(申请人提供)：昼夜节律系统与睡眠/醒来周期之间的不一致会产生许多生理问题(例如，失眠、嗜睡、认知减退、胃肠道不适、长期健康风险)，这些问题通常与夜班工作、清晨工作、时差以及延迟睡眠相障碍(DSPD)等基于昼夜节律的睡眠障碍有关。这些健康和安全的减少对个人和公共健康和安全构成了重大威胁。在这项资助的过程中，我们研究了相移(重置)人类昼夜节律的治疗方法，以消除或减弱昼夜节律失调。在这样做的过程中，在阶段推进(节奏设定得较早)和阶段延迟(节奏设定较晚)的大小上出现了意想不到的种族差异；非裔美国人(“黑人”)与高加索人(“白人”)相比，表现出更大的阶段推进和更小的阶段延迟。这些数据与我们的观察一致，即黑人比白人表现出更短的内源性自由奔跑的昼夜节律周期(Tau)。较短的时间段使其更容易推进，但更难推迟。这些潜在的昼夜生理学差异表明，黑人和白人对现实世界中昼夜节律失调的情况(例如，轮班工作或时差)的反应不同，这取决于睡眠转移的方向。我们提出了第一个前瞻性设计的研究，以检查昼夜节律相移和与昼夜节律失调相关的症状严重程度的种族差异。将有两项研究。每项研究将从5天开始，其中包括3天的超传统睡眠-觉醒、明-暗(LD)周期(4小时强制去同步)，以确定昼夜节律。然后，在几个基准日之后，睡眠时间表将提前9小时(研究1，阶段推进)或9小时后(研究2，阶段延迟)，持续3天。在每项研究中，唾液褪黑素采样以确定暗光褪黑素的开始(DLMO)将发生在超LD周期之前和之后，以确定昼夜节律周期以及在天数错位、睡眠偏移前后确定相移的幅度。将在基线和睡眠失调期间检查认知表现、警觉性、幸福感以及睡眠质量和数量，以确定与昼夜失调相关的症状严重程度。我们假设，在研究1(阶段推进)中，黑人的昼夜节律周期将比白人短，在研究2(阶段延迟)中，白人将比黑人的阶段延迟更多。我们还预测，当睡眠时间表被推迟时，黑人的觉醒功能以及睡眠质量和数量比白人更大的减少，而当睡眠时间表提前时，白人比黑人更大的减少。该项目不仅将扩大我们对人类生物钟基本原理的了解，还将为基于生物钟的睡眠障碍的治疗提供信息，并强调在确定最佳治疗策略时需要考虑种族因素。

DESCRIPTION (provided by applicant): Misalignment between the circadian timing system and the sleep/wake cycle produces many physiological problems (e.g., insomnia, sleepiness, cognitive decrements, gastrointestinal distress, long-term health risks), which are often associated with night shift work, early morning work shifts, jet lag, and circadian-based sleep disorders like delayed sleep phase disorder (DSPD). These health and safety decrements pose a significant threat to personal and public health and safety. Over the course of this grant, we have examined treatments to phase shift (reset) human circadian rhythms in order to eliminate or attenuate circadian misalignment. In doing so, an unexpected racial difference in the size of phase advances (when rhythms are set earlier) and phase delays (rhythms set later) emerged; African Americans ("Blacks") showed larger phase advances and smaller phase delays compared to Caucasians ("Whites"). These data are consistent with our observation that Blacks manifest shorter endogenous free-running circadian periods (tau) compared to Whites. Shorter periods make it easier to advance, but more difficult to delay. These differences in underlying circadian physiology suggest that Blacks and Whites respond differently to real-world situations of circadian misalignment (e.g., shift work or jet lag), depending on the direction that sleep is shifted. We propose the first prospectively designed studies to examine racial differences in circadian phase shifting and in symptom severity associated with circadian misalignment. There will be two studies. Each study will start with 5 days containing 3 days of an ultradian sleep-wake, light-dark (LD) cycle (4 h forced desynchrony) to determine circadian period. Then, after several baseline days, the sleep schedule will be shifted 9 h earlier (Study 1, Phase Advance) or 9 h later (Study 2, Phase Delay) for three days. In each study, salivary melatonin sampling to determine the dim light melatonin onset (DLMO) will occur before and after the ultradian LD cycle to determine circadian period and before and after the days of misaligned, shifted sleep to determine the magnitude of phase shifts. Cognitive performance, alertness, well-being, and sleep quality and quantity will be examined at baseline and during the days of misaligned sleep to determine symptom severity associated with circadian misalignment. We hypothesize that Blacks will have a shorter circadian period than Whites, will phase advance more than Whites in Study 1 (Phase Advance), and that Whites will phase delay more than Blacks in Study 2 (Phase Delay). We also predict greater decrements of waking function, and sleep quality and quantity in Blacks compared to Whites when the sleep schedule is delayed and greater decrement in Whites compared to Blacks when the sleep schedule is advanced. This project will not only expand our knowledge of basic principles of the human circadian clock, but will also inform treatment of circadian-based sleep disorders, and highlight the need to consider race when determining the optimal treatment strategies.