Treatment of Circadian Sleep Disorders with Bright Light

用强光治疗昼夜节律睡眠障碍

• 批准号: 7922051
• 负责人: STEVEN W LOCKLEY
• 金额: $ 27.96万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7922051
• 关键词: Acute; Address; Affect; Aging; Alzheimer' s Disease; Biological; Characteristics; Circadian Dysregulation; Circadian Rhythm Sleep Disorders; Circadian Rhythms; Color; Color Visions; Delayed Sleep Phase Syndrome; Development; Disease; Electroencephalogram; Electroencephalography; Ensure; Environment; Exposure to; Fatigue; Foundations; Frequencies; Future; Grant; Health; Home environment; Human; Image; Individual; Investigation; Jet Lag Syndrome; Knowledge; Light; Lighting; Literature; Mammals; Measurement; Mediating; Melatonin; Methods; Middle Insomnia; Modeling; Occupational; Pattern; Performance; Phase; Phase response curves; Photoperiod; Photoreceptors; Phototherapy; Physiologic pulse; Production; Property; Regimen; Relative (related person); Research Personnel; Retinal Cone; Role; Seasonal Affective Disorder; Shapes; Shift-Work Sleep Disorder; Sleep; Sleep Disorders; Source; Space Explorations; Space Flight; Stimulus; Strigiformes; System; Technology; Testing; Therapeutic; Time; Travel; Vertebrate Photoreceptors; Vision; Visual; Work; age related; alertness; base; circadian pacemaker; design; improved; light effects; neurobehavioral; new technology; novel; programs; research study; response; retinal rods; shift work; solid state

DESCRIPTION (provided by applicant): Light is a primary synchronizer of the human circadian pacemaker, with the response to light dependent on the timing, number, intensity, duration, and pattern of exposures. The timing of a light stimulus relative to circadian phase has particularly important practical implications in a real-world therapeutic setting, because inappropriately timed light exposure can cause an opposite phase resetting response to that desired. In prior years of this grant, we quantified the relationship between the timing of white light exposure and its circadian resetting effect in Phase Response Curves (PRC). These PRCs have provided the basis for designing appropriately-timed lighting regimes to reset the circadian pacemaker in a range of therapeutic applications. Recent studies have demonstrated that novel photoreceptors with a peak sensitivity in the shorter (blue) wavelengths, rather than rods and cones, are primarily responsible for mediating non-image forming responses such as circadian phase resetting and melatonin suppression. This has dramatic implications for using light to treat circadian rhythm disorders and other conditions. Current lighting is designed for the visual photopic system (peak sensitivity 555 nm), making most current lighting inappropriate for optimizing circadian responses. The development of solid-state lighting will make it possible to easily alter the spectral composition of light, such that light spectra could be tailored to the desired biological effect. Given that solid- state lighting for home and occupational settings will be introduced widely over the next decade, it is vital that we understand the fundamental aspects of how this new technology can be used to benefit human health. We have proposed a study in which we will systematically assess the circadian phase-shifting, melatonin suppressing, and alertness-enhancing response to a monochromatic light stimulus, using a wavelength (460 nm) that has been shown to maximally stimulate the circadian system. We will assess the phase-dependent response to this optimal light source (Aim I). We will examine the relationship between the melatonin- suppressing effects of the stimulus and its acute alerting and performance-enhancing effects in order to determine whether these effects are phase-dependent (Aims II and III), and whether the alerting and performance-enhancing effects are correlated with the degree of melatonin suppression (Aim II). We will examine changes in the EEG frequency power distribution to determine whether acute responses to the stimulus differentially affect the EEG spectrum at different times of day (Aim III). The results of this work will build the foundation for the application of new solid-state lighting technology for the phototherapy treatment of delayed sleep phase disorder, advanced sleep phase disorder, shift-work sleep disorder, jet lag, seasonal affective disorder, "sundowning" in Alzheimer's Disease, and age-related sleep maintenance insomnia.

描述（由申请人提供）：光是人类昼夜节律起搏器的主要同步器，对光的响应取决于暴露的时间、数量、强度、持续时间和模式。光刺激相对于昼夜节律相位的时间安排在现实世界的治疗环境中具有特别重要的实际意义，因为不适当的定时光照射可能会导致与所需的相反的相位重置反应。在这项资助的前几年，我们在相位响应曲线（PRC）中量化了白光照射时间与其昼夜节律重置效果之间的关系。这些 PRC 为设计适当定时的照明方案提供了基础，以在一系列治疗应用中重置昼夜节律起搏器。最近的研究表明，在较短（蓝色）波长下具有峰值灵敏度的新型光感受器（而不是视杆细胞和视锥细胞）主要负责介导非图像形成反应，例如昼夜节律相位重置和褪黑激素抑制。这对于利用光治疗昼夜节律紊乱和其他疾病具有重大意义。当前的照明是针对视觉明视系统（峰值灵敏度 555 nm）而设计的，使得大多数当前的照明不适合优化昼夜节律响应。固态照明的发展将使轻松改变光的光谱组成成为可能，从而可以根据所需的生物效应定制光谱。鉴于家庭和职业环境中的固态照明将在未来十年内广泛采用，我们了解如何利用这项新技术造福人类健康的基本方面至关重要。我们提出了一项研究，其中我们将系统地评估昼夜节律相移、褪黑激素抑制和对单色光刺激的警觉性增强反应，使用已被证明可以最大限度地刺激昼夜节律系统的波长（460 nm）。我们将评估对此最佳光源的相位相关响应（目标 I）。我们将检查刺激的褪黑激素抑制作用与其急性警觉和性能增强效果之间的关系，以确定这些效果是否具有阶段依赖性（目标 II 和 III），以及警觉和性能增强效果是否与褪黑激素抑制程度相关（目标 II）。我们将检查脑电图频率功率分布的变化，以确定对刺激的急性反应是否对一天中不同时间的脑电图频谱产生不同的影响（目标 III）。这项工作的成果将为新型固态照明技术应用光疗治疗延迟性睡眠相位障碍、提前睡眠相位障碍、轮班睡眠障碍、时差反应、季节性情感障碍、阿尔茨海默病的“日落”以及与年龄相关的睡眠维持性失眠等奠定基础。

项目成果

Treatment of Circadian Rhythm Sleep Disorders with Light

用光治疗昼夜节律睡眠障碍

• DOI: 10.47102/annals-acadmedsg.v37n8p669
• 发表时间: 2008
• 期刊: Annals of the Academy of Medicine, Singapore
• 作者: Lisa Y. M. Chuah;M. Chee
• 通讯作者: M. Chee

Circadian lipid and hepatic protein rhythms shift with a phase response curve different than melatonin.

• DOI: 10.1038/s41467-022-28308-6
• 发表时间: 2022-02-03
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Kent BA;Rahman SA;St Hilaire MA;Grant LK;Rüger M;Czeisler CA;Lockley SW
• 通讯作者: Lockley SW

The timing of the human circadian clock is accurately represented by the core body temperature rhythm following phase shifts to a three-cycle light stimulus near the critical zone.

人体生物钟的时间由核心体温节律准确地表示，随后相移到关键区域附近的三周期光刺激。

• DOI: 10.1177/074873040001500609
• 发表时间: 2000
• 期刊: Journal of biological rhythms
• 影响因子: 3.5
• 作者: KhalsaSBS;Jewett,ME;Duffy,JF;Czeisler,CA
• 通讯作者: Czeisler,CA

Relationship of endogenous circadian melatonin and temperature rhythms to self-reported preference for morning or evening activity in young and older people.

• 发表时间: 1999-03
• 期刊: Journal of investigative medicine : the official publication of the American Federation for Clinical Research
• 作者: J. Duffy;D. Dijk;Edward F. Hall;C. Czeisler

Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light.

人类昼夜节律系统的光谱响应取决于辐照度和暴露在光下的持续时间。

• DOI: 10.1126/scitranslmed.3000741
• 发表时间: 2010-05-12
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Gooley JJ;Rajaratnam SM;Brainard GC;Kronauer RE;Czeisler CA;Lockley SW
• 通讯作者: Lockley SW