Racial Differences in Human Circadian Rhythms

人类昼夜节律的种族差异

• 批准号: 8525458
• 负责人: CHARMANE I EASTMAN
• 金额: $ 51.91万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-07 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8525458
• 关键词: 4-aminospiroperidol; Address; African American; Attenuated; Beds; Birds; Caucasians; Caucasoid Race; Chronic; Circadian Rhythms; Cognitive; Data; Diagnosis; Disease; Distress; Flying body movement; Frequencies; Genes; Grant; Health; Hour; Human; Individual; Jet Lag Syndrome; Knowledge; Light; Malignant Neoplasms; Measures; Melatonin; Performance; Personal Satisfaction; Phase; Physiological; Physiology; Prevalence; Public Health; Race; Recommendation; Reporting; Research Design; Risk; Running; Safety; Salivary; Sampling; Schedule; Severities; Single Nucleotide Polymorphism; Sleep; Sleep Disorders; Sleep Wake Cycle; Sleeplessness; Strigiformes; Symptoms; System; Testing; Time; Travel; alertness; base; circadian pacemaker; gastrointestinal; improved; phase 1 study; phase 2 study; racial difference; response; shift work; tau Proteins; treatment strategy

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）：昼夜节律系统与睡眠/觉醒周期之间的失调会产生许多生理问题（例如失眠、嗜睡、认知能力下降、胃肠道不适、长期健康风险），这些问题通常与夜班工作、清晨轮班、时差反应和基于昼夜节律的睡眠障碍（如睡眠相位延迟障碍（DSPD））有关。这些健康和安全下降对个人和公共健康与安全构成重大威胁。在这笔资助的过程中，我们研究了相移（重置）人类昼夜节律的治疗方法，以消除或减轻昼夜节律失调。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（节奏设置较晚时）大小方面意想不到的种族差异；与白种人（“白人”）相比，非裔美国人（“黑人”）表现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结果一致，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)。周期越短，推进就越容易，但拖延就越困难。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失调的现实情况（例如轮班工作或时差反应）的反应不同，具体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以及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，其中包含 3 天的超昼夜睡眠-觉醒、明暗 (LD) 周期（4 小时强制不同步），以确定昼夜节律周期。然后，在几个基线天后，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，将在超日 LD 周期之前和之后进行唾液褪黑激素采样以确定弱光褪黑激素发作 (DLMO)，以确定昼夜节律周期，以及在错位、移位睡眠的日子之前和之后进行以确定相移的幅度。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（相位提前）中比白人相位提前更多，在研究 2（相位延迟）中白人比黑人相位延迟更多。我们还预测，当睡眠时间推迟时，黑人的清醒功能、睡眠质量和数量会比白人有更大的下降，而当睡眠时间提前时，白人的觉醒功能、睡眠质量和数量会比黑人有更大的下降。该项目不仅将扩展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。