Racial Differences in Human Circadian Rhythms

描述（由申请人提供）：昼夜节律系统与睡眠/觉醒周期之间的不一致会产生许多生理问题（例如失眠、嗜睡、认知能力下降、胃肠不适、长期健康风险），这些问题通常与夜班工作、清晨轮班、时差和基于昼夜节律的睡眠障碍（如延迟睡眠阶段障碍（DSPD））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，一个意想不到的种族差异在阶段推进（节奏设置得更早）和阶段延迟（节奏设置得更晚）的大小上出现了；非裔美国人（“黑人”）与白种人（“白人”）相比，表现出更大的相位提前和更小的相位延迟。这些数据与我们的观察一致，即与白人相比，黑人表现出更短的内源性自由运行昼夜节律周期（tau）。时间越短，进步就越容易，但拖延就越困难。这些潜在生理昼夜节律的差异表明，黑人和白人对生理昼夜节律失调的现实情况（例如，倒班工作或时差）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。每项研究将开始5天，其中包括3天的超昼夜睡眠-觉醒，光-暗（LD）周期（4小时强制非同步），以确定昼夜节律周期。然后，在几个基准日之后，睡眠时间表将提前9小时（研究1，阶段提前）或推迟9小时（研究2，阶段延迟），持续三天。在每项研究中，唾液褪黑素采样以确定在超昼夜LD周期前后发生的暗光褪黑素发作（DLMO），以确定昼夜节律周期，以及在错位、移位睡眠的日期前后确定相移幅度。认知表现、警觉性、幸福感、睡眠质量和睡眠时间将在基线和睡眠失调期间进行检查，以确定与昼夜节律失调相关的症状严重程度。我们假设黑人的昼夜节律周期比白人短，在研究1（阶段提前）中比白人的阶段提前多，在研究2（阶段延迟）中白人的阶段延迟比黑人多。我们还预测，当睡眠时间被推迟时，黑人的清醒功能、睡眠质量和睡眠量的下降幅度比白人大，而当睡眠时间被提前时，白人的下降幅度比黑人大。该项目不仅将扩大我们对人类生物钟基本原理的了解，而且还将为基于昼夜节律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考虑种族的必要性。

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.