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

项目摘要 在美国，大多数年龄较大的青少年长期睡眠不足，比同龄人少睡1- 2小时。 推荐随着青春期的进展，昼夜节律（~24小时）系统的变化较晚（延迟）;这种变化 会导致大龄青少年的晚睡。早期的学校开始时间迫使青少年更早起床 比他们的自发觉醒时间更长。因此，睡眠的机会缩短。许多青少年也 在“错误的”生理节奏时间起床上学。慢性昼夜节律失调和睡眠限制 他们的高峰期在青春期后期，并与早晨白天嗜睡，学习成绩差， 表现、行为问题、抑郁情绪、自杀意念、物质使用、胰岛素抵抗，以及 肥胖来自灯箱的强光照射可以更早地改变节奏（相位提前），以促进更早的节奏。 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 年龄较大的青少年对强光的相位响应曲线（PRCs）。为了使昼夜节律提前，我们 PRCs显示，理想的开始光照时间略早于唤醒时间， 避免在睡前，因为这是光产生最大相位延迟偏移的时候。一个意想不到 然而，从我们的结果中发现，第二个推进区在下午（习惯性出血后约6至9小时）。 唤醒时间），这表明下午的光可能比白天的光具有更强的昼夜节律相位推进能力。 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发现 并测试单独定时的下午光以及与早晨明亮的光相结合是否可以改变 14至17岁的青少年的昼夜节律更早。四组将在一个 随机平行组设计：午后强光，早晨强光，早晨+午后强光， 和一个昏暗的房间灯光控制。青少年将完成为期2周的方案。经过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生活4天。睡眠/黑暗和明亮的光的时间 暴露将逐渐提前。明亮的灯光（~5000勒克斯）将根据他/她的马厩单独计时 基线睡眠时间表第一次3小时早晨强光暴露将在第一天醒来前1小时开始 早上第一个3小时的下午强光暴露将在醒来后开始6小时。上午+下午 曝光将在相同的时间开始开始，但每次曝光将为1.5小时，以便每次曝光总共3小时的强光。 除暗光对照组外，其余各组均给予日。生物钟的相移 由昏暗的灯光褪黑激素起效（DLMO）的主要结果。我们假设下午的强光 提前DLMO超过昏暗的室内光线，下午明亮的光线将与早晨明亮的光线协同工作 光产生更大的变化比上午或下午明亮的光单独。如果我们的假设成立， 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。 之前

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.