Racial Differences in Human Circadian Rhythms

描述（由申请人提供）：昼夜节律计时系统和睡眠/唤醒周期之间的不对准产生许多生理问题（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期障碍（DSPD）有关。这些健康和安全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，以消除或减弱昼夜失调。在这样做的过程中，出现了相位提前（当节奏设置较早时）和相位延迟（节奏设置较晚）的大小的意外种族差异;非洲裔美国人（“黑人”）与高加索人（“白人”）相比显示出较大的相位提前和较小的相位延迟。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的昼夜节律周期（tau）。时间越短，推进越容易，拖延越难。这些潜在的昼夜节律生理学差异表明，黑人和白人对昼夜节律失调的现实情况的反应不同（例如，轮班工作或时差），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，以检查种族差异的昼夜节律相移和症状的严重程度与昼夜节律失调。将有两项研究。每项研究将从5天开始，包括3天的超昼夜睡眠-觉醒、明-暗（LD）周期（4小时强迫睡眠），以确定昼夜节律周期。然后，在几个基线日后，睡眠时间表将提前9小时（研究1，相位提前）或推迟9小时（研究2，相位延迟），持续3天。在每项研究中，唾液褪黑激素采样，以确定昏暗的光褪黑激素发作（DLMO）将发生之前和之后的超昼夜LD周期，以确定昼夜节律周期和之前和之后的日子错位，移位睡眠，以确定相移的幅度。将在基线和失调睡眠期间检查认知表现、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中相位提前比白人多（相位提前），在研究2中白人相位延迟比黑人多（相位延迟）。我们还预测更大的递减的觉醒功能，睡眠质量和数量的黑人相比，白人的睡眠时间表被延迟和更大的递减白人相比，黑人的睡眠时间表是先进的。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需要考虑种族。

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.