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，在许多情况下，人类的昼夜节律与所需的睡眠/唤醒时间表未对准。喷气式旅行，夜班工作，清晨轮班工作，并且仅在周末晚些时候睡觉或度假后睡觉的星期一早上返回正常工作或学校时间表，这一切都可能导致昼夜节律的错位。这种错位会产生各种症状，包括白天嗜睡，警报降低，失眠，慢性部分睡眠剥夺和胃肠道痛。明亮的光和褪黑激素都能够重置或移动昼夜节律，并已用于帮助人们适应所需的睡眠/唤醒时间表。各种褪黑激素剂量和轻盒的商业，非处方的可用性突出了消费者对简单，无创，家庭治疗的渴望，以治疗与昼夜节律相关的睡眠障碍。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感受器检测光，尽管杆和锥体也提供了一些输入。行业已经大写了这一发现，现在可以使用蓝色灯箱。但是，为了从褪黑激素药丸或轻盒中获得最大的收益，必须了解其最佳给药时间。相位响应曲线（PRC）在整个24小时内在不同时间呈现时描述了对特定刺激的相位转移响应。我们建议将PRC生成非处方，市售的相位转移产品：褪黑激素药和灯箱。因此，我们的研究结果将产生直接的实用建议。我们将生成4个PRC：1）0.5 mg褪黑激素，2）3.0 mg褪黑激素，3）明亮的白光和4）中等强度蓝光。我们将使用一种新颖，有效的协议，其中受试者通过超大的浅色/唤醒时间安排（4小时）进行自由运行，并且我们将在整个昼夜节律周期中在各个点上应用褪黑激素或光。我们将使用内源性褪黑激素节奏作为昼夜节律的标记，以计算褪黑激素或光的给药时间。中国将告诉我们何时施用这些相位转移刺激以实现所需方向的最大相移，并且在这些产品中使用这些产品将在错误的方向上诱导相移，并应避免。需要此信息，以便专业人员可以向患者和其他消费者提出最佳建议。此外，PRC的比较还可以揭示有关人类昼夜节律系统的信息，例如褪黑激素和光的相对相位转移能力或光感受器对昼夜节律系统的相对贡献。