Racial Differences in Human Circadian Rhythms

人类昼夜节律的种族差异

基本信息

批准号：
9064638
负责人：
CHARMANE I EASTMAN
金额：
$ 52.07万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-07 至 2018-05-31
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：昼夜节律时机系统与睡眠/唤醒周期之间的错位会导致许多生理问题（例如失眠症，嗜睡，认知能力下降，胃肠道遇险，长期健康风险），这些生理问题通常与夜班工作，早晨的工作偏移，落后的睡眠不良阶段相关，这些工作通常与夜班工作相关。这些健康和安全降低对个人和公共健康和安全构成了重大威胁。在这笔赠款的过程中，我们检查了以消除或减轻昼夜节律失误的方式进行相位转移（重置）人类昼夜节律的治疗方法。这样一来，出现了相位进步的大小（较早设置节奏）和相位延迟（稍后设置的节奏）的意外种族差异；与高加索人（“白人”）相比，非裔美国人（“黑人”）表现出更大的阶段进步和较小的阶段延误。这些数据与我们的观察结果一致，即黑人与白人相比表现出较短的内源性自由漫画时期（TAU）。较短的时期使进步更容易，但更难延迟。这些潜在昼夜节律生理学的差异表明，黑人和白人对昼夜节律未对准现实情况的反应不同（例如，移位工作或喷气滞后），具体取决于睡眠的方向。我们提出了第一个前瞻性设计的研究，以检查昼夜节期转移以及与昼夜节律错位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，其中包含超过3天的超级睡眠觉醒，浅黑色（LD）周期（4小时）以确定昼夜节律时期。然后，经过几天后，睡眠时间表将早于9小时（研究1，阶段进步）或9小时（研究2，相延迟）进行三天。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）将发生在超大LD循环之前和之后，以确定昼夜节律时期以及未对准的，偏移的睡眠时间之前和之后，以确定相位移位的幅度。认知表现，机敏性，福祉以及睡眠质量和数量将在基线和睡眠未对准的日子里进行检查，以确定与昼夜节律错位相关的症状严重程度。我们假设黑人的昼夜节日时间比白人的时间要短，比研究1（阶段进步）的阶段进步要多，并且白人比研究2（相位延迟）中的黑人比黑人多。与白人相比，与黑人相比，与黑人相比，与黑人相比，与黑人相比，与黑人相比，我们还可以预测黑人醒来功能的降低，黑人的睡眠质量和数量的降低，而睡眠时间表则降低了。该项目不仅会扩大我们对人类昼夜节律时钟基本原理的了解，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。