Adolescent circadian misalignment: Mechanistic studies of sleep and light

项目摘要 随着青春期的进展，生物钟移得更晚（延迟）;这种变化有助于晚睡眠， 年长的青少年。然而，早期的学校开始时间迫使青少年比他们自发的更早起床。 醒来的时间和睡眠的机会缩短。事实上，美国的大多数青少年长期 睡眠不足，睡眠时间比建议少1- 2小时。此外，许多青少年在早上起床上学。 “错误的”昼夜节律时间。慢性昼夜节律失调和睡眠限制在晚些时候达到顶峰 青少年，并与早晨白天嗜睡，学习成绩差，行为 问题，抑郁情绪，自杀意念，物质使用和肥胖。早晨明亮的光线照射， 灯箱可以更早地改变节奏（相位提前），以促进更早的睡眠开始，并减少昼夜节律 不一致和相关风险。我们构建了第一个相位响应曲线（PRC）的光， 青少年和确定的最佳时间为明亮的光暴露，以产生相位提前约1 在习惯性的起床和睡觉前应该避免光线，因为它会导致 延迟（delay）。然而，对成年人的研究表明，限制睡眠和暴露于 晚睡带来的夜间光线--青少年睡眠的两个典型特征--使早晨的光线明亮 在生产进步方面效率较低。我们在青少年中的试点数据模拟了这一发现，但也表明， 在正常的家庭照明和随后的睡眠限制之前和期间， 早晨明亮的光线方案，可以在错误的方向上移动系统（相位延迟）。的首要目标 这项建议是为了检查睡眠限制和夜间家庭照明的剂量， 14-17岁青少年的相位提前到早晨明亮的光线。研究1建议构建一个睡眠 限制与正常家庭晚上光剂量反应曲线，以确定在该点，早晨 明亮的光线开始失去效力。在一周的基础睡眠时间为10小时后， 参与者将保持相同的起床时间，但被随机分配到4个就寝时间之一，这将是 与基线相同或晚于基线，以产生4个水平的夜间光照睡眠限制（0、1.5、3或4.5小时）。后 2个晚上，我们将逐渐将睡眠时间表提前3个晚上，参与者将获得明亮的光线 每天早上我们假设昼夜节律系统将随着充足的睡眠而发展，但随着睡眠时间的增加， 睡眠限制/夜间光照，尽管相位提前，昼夜节律将不会改变或延迟 早晨明亮的光。研究2将测试戴太阳镜是否能减少晚上的光照 睡前限制睡眠可以促进相位提前。研究2将测试相同的4个“剂量”的 睡眠限制建立剂量-反应曲线的主要结果测量将是 中央昼夜节律钟由昏暗光褪黑激素起始（DLMO）和总睡眠时间标记， 实验室中的腕动记录仪。次要结果包括认知表现、嗜睡和情绪。

PROJECT SUMMARY Circadian clocks shift later (delay) with the progression of puberty; this shift contributes to late sleep onsets in older adolescents. Early school start times, however, force teenagers awake earlier than their spontaneous wake time and the opportunity for sleep shortens. Indeed, a majority of adolescents in the U.S. are chronically sleep deprived, getting 1- 2 h less sleep than recommended. Also, many adolescents wake 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, and obesity. Morning bright light exposure from light boxes can shift rhythms earlier (phase advance) to facilitate earlier sleep onset, and reduce circadian misalignment and the associated risks. We constructed the first phase response curve (PRC) to light for adolescents and determined that the optimal time for bright light exposure to produce phase advances was ~1 h before habitual wake and light should be avoided around the time of habitual bedtime because it causes rhythms to shift later (delay). Studies of adults, however, indicate that restricted sleep and exposure to evening light due to late bedtimes – two classic features of older adolescent sleep – make morning bright light less effective in producing advances. Our pilot data in adolescents mimic this finding, but also suggest that staying awake late in normal household lighting and the subsequent sleep restriction before and during a 3-day morning bright light regimen, can shift the system in the wrong direction (phase delay). The overarching goal of this proposal is to examine the DOSE of sleep restriction and evening household light that prevents the desired phase advance to morning bright light in adolescents aged 14-17 years. Study 1 proposes to construct a sleep restriction with normal household evening light dose-response curve to determine the point at which morning bright light begins to lose its effectiveness. Following a baseline week with 10-h sleep opportunities, participants will keep the same wake time but be randomly assigned to one of 4 bedtimes which will be the same or later than baseline to produce 4 levels of sleep restriction with evening light (0, 1.5, 3, or 4.5 h). After 2 nights, we will gradually shift the sleep schedule earlier for 3 nights, and participants will receive bright light each morning. We hypothesize that the circadian system will advance with sufficient sleep, but with increasing sleep restriction/evening light, circadian rhythms will not shift or will delay despite the phase advancing morning bright light. Study 2 will test whether attenuating evening light exposure by wearing sunglasses before bedtime during sleep restriction can facilitate phase advances. Study 2 will test the same 4 “doses” of sleep restriction. The main outcome measures to build the dose-response curves will be phase shifts of the central circadian clock marked by the dim light melatonin onset (DLMO) and total sleep time measured from wrist actigraphy in the laboratory. Secondary outcomes include cognitive performance, sleepiness, and mood.