Adolescent circadian phase shifts: novel time-of-day targets for bright light

青少年昼夜节律相移：新的亮光时间目标

• 批准号: 10224325
• 负责人: Stephanie Crowley McWilliam
• 金额: $ 50.2万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10224325
• 关键词: Address; Adolescence; Adolescent; Adult; Alcohol consumption; Anxiety; Biological; Chronic; Circadian Rhythms; Circadian desynchrony; Conflict (Psychology); Control Groups; Cues; Data; Depressed mood; Development; Drowsiness; Emotions; Feeling suicidal; Future; Goals; Home; Individual; Insulin Resistance; Laboratories; Lead; Light; Measures; Melatonin; Obesity; Outcome; Overweight; Participant; Performance; Phase; Phase response curves; Phototherapy; Protocols documentation; Psychosocial Factor; Puberty; Publishing; Randomized; Recommendation; Risk; Risk Behaviors; Schedule; Schools; Sleep; Sleep Deprivation; Sunlight; System; Teenagers; Testing; Time; Work; aged; awake; base; circadian; circadian pacemaker; conduct problem; design; experience; falls; follow-up; novel; response; sleep onset; substance use

PROJECT SUMMARY A majority of older adolescents in the U.S. are chronically sleep deprived, getting 1- 2 h less sleep than recommended. The circadian (~24-h) system shifts later (delay) with the progression of puberty; this shift contributes to late sleep onsets in older adolescents. Early school start times force teenagers awake earlier than their spontaneous wake time. Thus, the opportunity for sleep shortens. Many adolescents are also waking for school at the “wrong” circadian time. Chronic circadian misalignment and sleep restriction are at their peak during late adolescence, and are associated with morning daytime sleepiness, poor academic performance, conduct problems, depressed mood, suicidal ideation, substance use, insulin resistance, and obesity. Bright light exposure from light boxes can shift rhythms earlier (phase advance) to facilitate earlier sleep onset, and reduce morning circadian misalignment and the associated risks. We constructed the first phase response curves (PRCs) to bright light in older adolescents. To phase advance circadian rhythms, our PRCs showed that the ideal time to begin light exposure was slightly before wake-up time and light should be avoided around bedtime because this is when light produces maximum phase delay shifts. An unexpected finding from our results, however, was a second advancing region in the afternoon (~6 to 9 h after habitual wake-up time) suggesting that afternoon light may have more circadian phase advancing ability than traditionally thought. The overall goal of this mechanistic study is to follow-up on our unexpected PRC findings and test whether individually-timed afternoon light alone and in combination with morning bright light can shift circadian rhythms earlier in older adolescents aged 14 to 17 years. Four groups will be compared in a randomized parallel group design: afternoon bright light, morning bright light, morning + afternoon bright light, and a dim room light control. Adolescents will complete a 2-week protocol. After a baseline week with a stable sleep schedule, adolescents will live in our laboratory for 4 days. Sleep/dark and the time of bright light exposure will gradually shift earlier. Bright light (~5000 lux) will be timed individually based on his/her stable baseline sleep schedule. The first 3-h morning bright light exposure will begin 1 h before wake on the first morning. The first 3-h afternoon bright light exposure will begin 6 h after wake. The morning + afternoon exposures will begin at the same times, but each exposure will be 1.5 h so that a total of 3 h of bright light per day will be given to each group except the dim light control group. Phase shifts of the circadian clocks marked by the dim light melatonin onset (DLMO) is the main outcome. We hypothesize that afternoon bright light will advance DLMO more than dim room light and afternoon bright light will work synergistically with morning bright light to produce larger shifts than morning or afternoon bright light alone. If our hypotheses are supported, these data will challenge the current understanding of how to use bright light to shift the circadian system earlier.

项目总结 美国大多数年龄较大的青少年长期睡眠不足，睡眠时间比 推荐的。昼夜节律(~24小时)系统随着青春期的进展而推迟(延迟)；这种转变 导致年龄较大的青少年入睡过晚。早起上课时间迫使青少年提早醒来 而不是他们的自发唤醒时间。因此，睡眠的机会缩短了。许多青少年也是 在“错误的”生物钟时间醒来去上学。慢性昼夜节律失调和睡眠受限 他们的高峰期在青春期晚期，并与早上白天嗜睡，学习成绩差有关 表现，行为问题，抑郁情绪，自杀念头，药物使用，胰岛素抵抗，以及 肥胖。来自灯箱的强光照射可以提前改变节律(相位提前)，以利于更早 睡眠开始，并减少早晨的昼夜节律失调和相关风险。我们建造了第一座 年龄较大的青少年对强光的相反应曲线。为了推进昼夜节律，我们的 PRCS显示，开始曝光的理想时间是在醒来时间之前的轻微时间，光线应该是 避免在睡前，因为这是光线产生最大相位延迟移位的时候。意想不到的 然而，从我们的结果中发现，第二个推进区在下午(习惯性后约6至9小时) 唤醒时间)，这表明下午的光线可能比 传统上认为。这项机械研究的总体目标是跟进我们在中华人民共和国的意外发现。 并测试单独计时的午后光线和与早上的强光结合是否可以转换 14至17岁年龄较大的青少年较早出现昼夜节律。四个小组将在一年中进行比较 随机平行分组设计：下午明灯，早上明灯，早上+下午明灯， 和一个昏暗的房间灯光控制。青少年将完成为期两周的方案。在经历了一个稳定的基线周后 睡眠时间表，青少年将在我们的实验室住4天。睡眠/黑暗和明亮的时间 风险敞口将在更早的时候逐渐转移。强光(~5000勒克斯)将根据他/她的稳定情况单独计时 基线睡眠时间表。第一次3小时的清晨强光照射将在第一次醒来前1小时开始。 早上。第一次3小时的午后强光照射将在觉醒后6小时开始。上午+下午 曝光将在相同的时间开始，但每次曝光将为1.5小时，因此每次曝光总共3小时的亮光 除暗光对照组外，每组都将有一天。昼夜节律钟表的相移 在昏暗的光线下，褪黑素起病(DLMO)是主要结局。我们假设下午会有明亮的光线 超前的DLMO比昏暗的房间光和下午的明亮光更能与早晨的明亮协同工作 光产生比上午或下午单独明亮的光更大的移位。如果我们的假设得到支持， 这些数据将挑战目前人们对如何利用强光改变昼夜节律系统的理解 早些时候。