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(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/醒来时间表不一致。乘坐飞机、上夜班、上早班，或者只是在周末晚些时候睡觉或度假后，在周一早上回到正常的工作或学校时间表上，都会导致生物钟失调。这种错位会产生一系列症状，包括白天嗜睡、警觉性下降、失眠、慢性部分睡眠不足和胃肠道不适。强光和褪黑素都能够重置或相移生物钟，并已被用来帮助人们适应他们想要的睡眠/醒来时间表。各种褪黑激素的商业非处方药和灯箱的供应突显了消费者对简单、非侵入性的家庭治疗方法的渴望，以治疗与昼夜节律有关的睡眠障碍。最近已经证明，昼夜节律系统主要使用一种新型的蓝光敏感的光感受器来探测光，尽管杆和锥体也提供一些输入。工业界已经利用了这一发现，现在已经有了蓝光盒。然而，为了从褪黑素药丸或灯箱中获得最大益处，了解它们的最佳给药时间是至关重要的。相位响应曲线描述了当特定刺激在24小时内的不同时间呈现时，对该特定刺激的相移响应。我们建议为非处方药、商业上可获得的相移产品：褪黑素药丸和灯箱产生PRC。因此，我们的研究结果将产生直接的实际建议。我们将产生4种原癌基因：1)0.5毫克褪黑素，2)3.0毫克褪黑素，3)明亮的白光，4)中等强度的蓝光。我们将使用一种新颖、高效的方案，让受试者自由运行一个极端的明-暗/醒-睡眠时间表(每天4小时)，我们将在整个昼夜周期的不同时间点应用褪黑素或光。我们将使用内源性褪黑素节律作为生物钟的标志，来计算相移和服用褪黑素或光的时间。PRC会告诉我们何时施加这些相移刺激以实现所需方向的最大相移，以及使用这些产品会导致错误方向相移的时间，应该避免。需要这些信息，以便专业人员能够向患者和其他消费者提供最佳建议。此外，对原癌基因的比较还可能揭示有关人类昼夜节律系统的信息，例如褪黑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。