Adolescent circadian misalignment: Mechanistic studies of sleep and light

项目总结 随着青春期的进展，生物钟移动得更晚(延迟)；这种变化导致睡眠开始晚 年龄较大的青少年。然而，早起的开学时间迫使青少年比他们自发的更早醒来 醒来的时间和睡觉的机会缩短了。事实上，美国大多数青少年都患有慢性病 睡眠不足，睡眠时间比推荐的少1-2小时。此外，许多青少年在学校起床上学。 “错误的”昼夜节律。慢性昼夜节律失调和睡眠受限在晚期达到顶峰 青春期，并与早上白天困倦，学习成绩差，品行 问题、抑郁情绪、自杀念头、药物使用和肥胖。早晨的强光暴露来自 灯箱可以更早地改变节奏(相位提前)，以促进更早的睡眠，并减少昼夜节律 错位及其相关风险。我们构建了光的第一相响应曲线(PRC) 并确定强光照射产生相位提前的最佳时间是~1 应避免在习惯性睡前醒来，并在习惯性就寝时间前后避免光照，因为这会导致 节奏要稍后改变(延迟)。然而，对成年人的研究表明，限制睡眠和接触 晚睡导致的晚光--这是年龄较大的青少年睡眠的两个典型特征--使早晨的光线明亮 在产生预付款方面效率较低。我们在青少年中的试验数据与这一发现相似，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保持清醒到很晚 晨光养生，会使系统向错误的方向移动(相位延迟)。的首要目标是 这项建议是为了检查睡眠限制和晚间家庭照明的剂量，以防止预期的 14-17岁青少年进入晨光阶段。研究1建议构建一种睡眠 限制用正常家庭晚间光照剂量-反应曲线来确定上午哪一点 强光开始失去它的效力。在有10小时睡眠机会的基线一周之后， 参与者将保持相同的起床时间，但被随机分配到4个睡觉时间中的一个，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(0、1.5、3或4.5h)的睡眠限制。之后 2个晚上，我们将逐步提前3个晚上的睡眠时间，参与者将得到明亮的光线 每天早上。我们假设，昼夜节律系统将在充足睡眠的情况下前进，但随着睡眠的增加 睡眠限制/晚间光线，昼夜节律不会改变或延迟，尽管相位提前 早晨阳光明媚。研究2将测试戴墨镜是否能减弱夜间日光照射 睡前限制睡眠可以促进阶段推进。研究2将测试相同的4个“剂量” 睡眠限制。建立剂量-反应曲线的主要观察指标将是 以暗光褪黑素开始(DLMO)和总睡眠时间为标志的中枢昼夜节律时钟 实验室里的手腕动作记录仪。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.