Adolescent circadian misalignment: Mechanistic studies of sleep and light

青少年昼夜节律失调：睡眠和光的机制研究

• 批准号: 10368967
• 负责人: Stephanie Crowley McWilliam
• 金额: $ 53.19万
• 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: 2020-04-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10368967
• 关键词: Adolescence; Adolescent; Adult; Age; Alcohol consumption; Alcohols; Attenuated; Beds; Behavior; Behavioral; Characteristics; Child; Chronic; Circadian Rhythms; Circadian desynchrony; Data; Depressed mood; Dose; Drowsiness; Drug usage; Effectiveness; Exposure to; Feeling suicidal; Goals; Health Personnel; Household; Impairment; Laboratories; Learning; Left; Light; Lighting; Measures; Melatonin; Moods; Nicotine; Obesity; Outcome; Outcome Measure; Parents; Participant; Performance; Phase; Phase response curves; Phototherapy; Problem Solving; Protocols documentation; Puberty; Randomized; Recommendation; Regimen; Risk; Risk-Taking; Satiation; Schedule; Schools; Side; Sleep; System; Teenagers; Testing; Time; Work; Wrist; Youth; actigraphy; aged; alertness; automobile accident; awake; base; circadian; circadian pacemaker; cognitive performance; conduct problem; cost effective; falls; improved; prevent; response; secondary outcome; sleep behavior; sleep onset; substance use; sunglasses; treatment guidelines; treatment strategy

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.

项目摘要 昼夜节律随后随着青春期的进展而移动（延迟）；这种转变有助于晚期入睡 年长的青少年。但是，早期的开始时间，迫使青少年早于赞助商 唤醒时间和睡眠的机会缩短。实际上，美国的大多数青少年在长期以来是长期的 睡眠加深，睡眠比建议的少1-2小时。此外，许多青少年在上学 “错”昼夜节时间。慢性昼夜节律的未对准和睡眠限制在后期达到顶峰 青少年，与早晨白天的嗜睡，学术表现不佳，行为相关 问题，情绪低落，自杀想法，使用物质和肥胖。早上明亮的光线 灯箱可以更早（阶段进步）改变节奏，以促进早期的睡眠开始，并减少昼夜节律 错位和相关风险。我们构建了第一相响应曲线（PRC） 青少年，并确定明亮光线暴露产生相位前进的最佳时间〜1 h在习惯性就寝时间时应避免习惯唤醒和灯光，因为它会导致 节奏以后移动（延迟）。然而，对成年人的研究表明，睡眠限制和暴露于 由于晚期的晚期而引起的夜灯 - 较旧的青春期睡眠的两个经典特征 - 使早晨明亮的光线 在产生进步方面效率较差。我们在青少年中的飞行员数据模仿了这一发现，但也表明 在正常的家庭照明和3天之前和期间的随后睡眠限制中保持清醒状态 早晨明亮的光方案，可以将系统朝错误的方向移动（相延迟）。总体目标 该建议是检查睡眠限制的剂量和夜间家庭光，以防止所需的 14-17岁的青少年的阶段前进到早晨的光线。研究1构建睡眠的建议 限制正常的家庭晚间光剂量响应曲线，以确定早晨 明亮的光开始失去其有效性。在基线周和10小时的睡眠机会之后， 参与者将保留相同的唤醒时间，但可以随机分配给4个床位之一，这将是 与基线相同或晚于基线，以产生4级的睡眠限制（0、1.5、3或4.5 h）。后 2晚，我们将逐渐改变睡眠时间表3晚，参与者将获得明亮的光线 每天早晨。我们假设昼夜节律的睡眠会进步，但随着增加 睡眠限制/晚上，昼夜节律不会改变或延迟阶段前进 早晨明亮的光线。研究2将测试是否戴太阳镜是否会衰减光线 在睡眠限制之前就睡前可以促进阶段进步。研究2将测试相同的4剂 睡眠限制。建立剂量响应曲线的主要结果指标将是 中央昼夜节律时钟以昏暗的光褪黑激素发作（DLMO）和总睡眠时间为标志 实验室中的腕部摄影。次要结果包括认知表现，嗜睡和情绪。