Adolescent circadian misalignment: Mechanistic studies of sleep and light

项目概要 随着青春期的进展，生物钟会变晚（延迟）；这种转变导致晚入睡 年龄较大的青少年。然而，提早上学时间迫使青少年比他们自然起床的时间更早起床。 醒来时间和睡眠机会缩短。事实上，美国的大多数青少年都长期处于 睡眠不足，睡眠时间比建议的时间少 1-2 小时。此外，许多青少年在学校起床去上学 “错误的”昼夜节律时间。慢性昼夜节律失调和睡眠限制在深夜达到顶峰 青春期，并与早晨白天困倦、学习成绩差、行为 问题、情绪低落、自杀意念、药物滥用和肥胖。早晨明亮的光线照射 灯箱可以更早地改变节律（相位提前），以促进更早的睡眠开始，并减少昼夜节律 错位和相关风险。我们构建了第一阶段光响应曲线（PRC） 青少年并确定亮光照射产生阶段提前的最佳时间为〜1 习惯性起床前的几个小时和习惯性就寝时间前后应避免光照，因为这会导致 节奏稍后转移（延迟）。然而，对成年人的研究表明，限制睡眠和接触 晚睡造成的夜间光线——老年青少年睡眠的两个典型特征——使早晨光线明亮 产生进步的效率较低。我们在青少年中的试点数据模仿了这一发现，但也表明 在正常的家庭照明下保持清醒，并在三天前和期间进行随后的睡眠限制 早晨明亮的光线养生法，可能会使系统转向错误的方向（相位延迟）。总体目标是 该提案旨在检查睡眠限制和晚间家庭灯光的剂量，以防止所需的睡眠 14-17 岁青少年的阶段提前到早晨明亮的光线。研究 1 提出构建一个睡眠 限制正常家庭夜间光剂量反应曲线，以确定早晨的点 明亮的光线开始失去效力。在基准周有 10 小时睡眠机会之后， 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 级夜间灯光睡眠限制（0、1.5、3 或 4.5 小时）。之后 2晚，我们将逐渐将睡眠时间提前3晚，参与者将接受明亮的灯光 每天早上。我们假设昼夜节律系统会随着充足的睡眠而进步，但随着睡眠的增加 睡眠限制/夜间光线，昼夜节律不会改变或延迟，尽管相位提前 早晨明亮的光线。研究 2 将测试佩戴太阳镜是否可以减弱夜间光线照射 睡前、睡眠期间限制可以促进阶段推进。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结果指标将是相移 中央生物钟以弱光褪黑激素开始 (DLMO) 和总睡眠时间为标志，测量时间为 实验室中的腕部体动记录仪。次要结果包括认知表现、困倦和情绪。

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.