Phase response curves for home remedies to treat circadian misalignment

治疗昼夜节律失调的家庭疗法的相位响应曲线

• 批准号: 7188687
• 负责人: CHARMANE I EASTMAN
• 金额: $ 37万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-05 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7188687
• 关键词: Advanced Sleep Phase Syndrome; Advertisements; Beds; Birds; Body Temperature; Boxing; Chronic Insomnia; Circadian Rhythms; Clinic; Delayed Sleep Phase Syndrome; Distress; Dose; Elderly; Future; General Population; Home Remedy; Home environment; Human; Industry; Invasive; Jet Lag Syndrome; Light; Measures; Melatonin; Middle Insomnia; Numbers; Outpatients; Patients; Phase; Phase response curves; Photoreceptors; Principal Investigator; Protocols documentation; Range; Recommendation; Relative (related person); Running; Schedule; Schools; Seasonal Affective Disorder; Shapes; Shift-Work Sleep Disorder; Sleep; Sleep Deprivation; Sleep Disorders; Sleep Wake Cycle; Societies; Stimulus; Strigiformes; Symptoms; System; Testing; Thinking; Time; Travel; Vertebrate Photoreceptors; Work; alertness; base; circadian pacemaker; cost; day; desire; gastrointestinal; innovation; light treatment; novel; pill; practical application; programs; response; shift work; sleep onset; young adult

DESCRIPTION (provided by applicant): In modern society, there are a number of situations in which human circadian rhythms are misaligned with the desired sleep/wake schedule. Jet travel, night shift work, early morning shift work and merely returning to a normal work or school schedule either on Monday morning after sleeping later on the weekend or after being on vacation can all result in circadian misalignment. This misalignment produces a wide range of symptoms including daytime sleepiness, decreased alertness, insomnia, chronic partial sleep deprivation, and gastrointestinal distress. Both bright light and melatonin are able to reset or phase shift the circadian clock, and have been used to help people adapt to their desired sleep/wake schedule. The commercial, over-the-counter availability of a wide range of melatonin doses and light boxes highlights the consumer's desire for simple, non-invasive, at-home treatments to treat circadian-related sleep disorders. Recently it has been demonstrated that the circadian system primarily detects light using a novel, blue-light-sensitive photoreceptor, although the rods and cones also provide some input. Industry has capitalized on this discovery, and blue light boxes are now available. However, in order to obtain maximum benefit from melatonin pills or light boxes it is essential to know their optimal administration time. Phase response curves (PRCs) describe the phase shifting response to a specific stimulus when it is presented at different times throughout the 24-h day. We propose to generate PRCs to over-the-counter, commercially available phase shifting products: melatonin pills and light boxes. Therefore, the results of our studies will yield direct practical recommendations. We will generate 4 PRCs: 1) 0.5 mg melatonin, 2) 3.0 mg melatonin, 3) bright white light, and 4) medium intensity blue light. We will use a novel, efficient protocol in which subjects free-run through an ultradian light-dark/wake-sleep schedule (4 h days), and we will apply melatonin or light at various points throughout the circadian cycle. We will use the endogenous melatonin rhythm as a marker of the circadian clock, to calculate phase shifts and the time of the administration of the melatonin or light. The PRCs will tell us when to administer these phase shifting stimuli to achieve the maximum phase shift in the desired direction, and also times at which use of these products would induce a phase shift in the wrong direction and should be avoided. This information is needed so that professionals can make the best recommendations to patients and other consumers. In addition, comparison of the PRCs may also reveal information about the human circadian system, such as the relative phase shifting abilities of melatonin and light or the relative contribution of photoreceptors to the circadian system.

描述（由申请人提供）：在现代社会中，有许多情况下，人类的昼夜节律与期望的睡眠/觉醒时间表不一致。坐飞机旅行、上夜班、上早班，或者周末睡得晚了，或者度假后回到正常的工作或上学时间，这些都可能导致昼夜节律失调。这种错位会产生一系列的症状，包括白天嗜睡、警觉性下降、失眠、慢性部分睡眠剥夺和胃肠道不适。明亮的光线和褪黑素都能够重置或相移生物钟，并被用来帮助人们适应他们想要的睡眠/觉醒时间表。各种剂量的褪黑激素和灯箱的商业化非处方供应，突显了消费者对简单、无创、在家治疗昼夜节律相关睡眠障碍的渴望。最近有研究表明，尽管视杆细胞和视锥细胞也提供了一些输入，但昼夜节律系统主要是通过一种新型的蓝光敏感光感受器来检测光。工业利用了这一发现，现在有了蓝色灯箱。然而，为了从褪黑素药片或灯箱中获得最大的益处，了解它们的最佳给药时间是必不可少的。相响应曲线（prc）描述了在24小时内不同时间出现的特定刺激的相移响应。我们建议将prc生产成非处方的、市售的相移产品：褪黑激素药片和灯箱。因此，我们的研究结果将产生直接的实用建议。我们将产生4种prc: 1) 0.5 mg褪黑素，2)3.0 mg褪黑素，3)明亮的白光，4)中等强度的蓝光。我们将使用一种新颖有效的方案，在该方案中，受试者自由运行一个超昼夜-黑暗/觉醒-睡眠时间表（4小时），我们将在整个昼夜周期的不同时间点使用褪黑激素或光照。我们将使用内源性褪黑激素节律作为生物钟的标记，来计算相移和褪黑激素或光的管理时间。prc将告诉我们何时管理这些相移刺激以实现所需方向上的最大相移，以及使用这些产品会导致错误方向上的相移的时间，并且应该避免。专业人员需要这些信息，以便向患者和其他消费者提出最佳建议。此外，prc的比较还可以揭示人类昼夜节律系统的信息，例如褪黑激素和光的相对相移能力或光感受器对昼夜节律系统的相对贡献。