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.

项目概要 美国大多数年龄较大的青少年长期睡眠不足，睡眠时间比正常青少年少 1 至 2 小时 受到推崇的。随着青春期的进展，昼夜节律（~24 小时）系统会延迟（延迟）；这种转变 导致年龄较大的青少年入睡较晚。提早上学迫使青少年提早起床 比他们自发醒来的时间。因此，睡眠的机会就会缩短。许多青少年也 在“错误的”昼夜节律时间起床去上学。慢性昼夜节律失调和睡眠限制 它们在青春期后期达到顶峰，并与早晨白天困倦、学业成绩不佳有关 表现、行为问题、情绪低落、自杀意念、药物滥用、胰岛素抵抗，以及 肥胖。灯箱的强光照射可以提前改变节奏（相位提前）以促进提前 睡眠开始，并减少早晨昼夜节律失调和相关风险。我们建造了第一个 老年青少年对强光的相位响应曲线（PRC）。为了逐步推进昼夜节律，我们 PRCs 表明，开始光照的理想时间是在醒来时间之前，并且光照应该是 避免在就寝时间前后使用，因为这是光产生最大相位延迟偏移的时间。一个意想不到的 然而，从我们的结果中发现，第二个前进区域是在下午（习惯性训练后约 6 至 9 小时） 醒来时间）表明下午的光线可能比白天有更多的昼夜节律提前能力 传统上认为。这项机制研究的总体目标是跟进我们意想不到的 PRC 研究结果 并测试单独定时的下午光以及与早晨明亮光的结合是否可以改变 14 至 17 岁的青少年的昼夜节律较早。四组将在一个 随机平行组设计：下午强光、上午强光、上午+下午强光、 和昏暗的房间灯光控制。青少年将完成为期两周的方案。经过一周稳定的基线后 睡眠时间表，青少年将在我们的实验室生活4天。睡眠/黑暗和明亮的光线时间 曝光将逐渐提前。明亮的光线（~5000 lux）将根据他/她的马厩单独计时 基线睡眠时间表。第一个 3 小时的早晨强光照射将在第一次醒来前 1 小时开始 早晨。第一个 3 小时的下午强光照射将于醒来后 6 小时开始。上午+下午 曝光将同时开始，但每次曝光时间为 1.5 小时，因此每次亮光总共 3 小时 除弱光对照组外，每组均给予一天的时间。标记的生物钟的相移 弱光褪黑激素发作（DLMO）是主要结果。我们假设下午的明亮光线会 先进的DLMO不仅仅是昏暗的室内光线和午后明亮的光线将与早晨明亮的光线协同工作 与仅早上或下午的强光相比，光产生更大的变化。如果我们的假设得到支持， 这些数据将挑战目前对如何利用强光改变昼夜节律系统的理解 早些时候。