Blue Light and Melatonin for Treatment of Circadian Rhythm Disorders and Jet Lag

描述（由申请人提供）：在许多情况下，现代人发现他们的昼夜节律与他们期望的睡眠/觉醒时间表不一致，例如在喷气式飞机旅行后、轮班工作期间以及在一些睡眠障碍中，例如睡眠相位延迟综合征。这种错位会导致过度疲劳、嗜睡、警觉性下降、注意力不集中、表现受损、睡眠缩短和中断、胃肠道不适，最终导致健康问题。明亮的光线和褪黑激素已经被用来帮助改变人类的生物钟，但很少有人对这种组合进行测试。最近令人兴奋的发现表明，昼夜节律系统使用了一种新的光感受器（除了视杆细胞和视锥细胞之外），它对短波长（蓝色）光最敏感，并且蓝光可以产生比其他波长更大的相移。我们将测试蓝色富集光和褪黑激素的组合，该方案适用于家庭和工作中的日常使用。在所有研究中，睡眠时间表将逐渐相位提前，在大多数研究中，下午将使用小剂量的褪黑激素，早上将使用明亮的蓝色富集光（来自单个灯箱），以帮助相位提前昼夜节律。我们的总体目标是以最少的努力产生最大可能的相位提前，同时保持昼夜节律与睡眠时间表保持一致，以防止副作用或时差症状。具体目标#1是确定蓝色富集光是否产生比白色光更大的相位超前。具体目标#2是评估下午褪黑激素和早晨明亮的富含蓝色的光对相位提前的相对贡献，并确定不需要灯箱的仅褪黑激素治疗是否有任何优点。具体目标#3是确定通过改变脉冲的持续时间和它们的数量，将相同的总持续时间的明亮的蓝色富集光分布到不同的图案中是否可以增加相位超前。具体目标#4是确定是否可以减少强光暴露的持续时间，同时仍然产生可接受的相移幅度。在所有研究中，将根据在昏暗光线下收集的完整褪黑激素曲线评估昼夜节律相位。我们还将测量睡眠（手腕活动监测器和日志），嗜睡和其他症状（问卷）和性能（计算机化）。这些研究将为生物钟的相移提供实用的建议，也可能提供有关人类生物钟如何对光做出反应的信息。

DESCRIPTION (provided by applicant): There are many situations in which modern humans find that their circadian rhythms are not aligned with their desired sleep/wake schedule, such as after jet travel, during shift work, and in some sleep disorders such as the delayed sleep phase syndrome. This misalignment causes excessive fatigue, sleepiness, decrements in alertness, loss of concentration, impaired performance, shortened and disrupted sleep, gastrointestinal distress and eventually health problems. Bright light and melatonin have been used to help phase shift the human circadian clock, but little has been done to test the combination. Recent exciting discoveries show that the circadian system uses a novel photoreceptor (besides the rods and cones) which is most sensitive to short wavelength (blue) light, and that larger phase shifts can be produced with blue light than with other wavelengths. We will test the combination of blue-enriched light and melatonin in a protocol that is practical for everyday use at home and at work. In all studies, the sleep schedule will be gradually phase advanced, and in most studies a small dose of melatonin will be used in the afternoon and bright blue-enriched light (from a single light box) will be used in the morning to help phase advance circadian rhythms. Our overall goal is to produce the largest possible phase advance with the least effort, while keeping the circadian rhythms aligned with the sleep schedule to prevent side-effects or jet-lag-type symptoms. Specific Aim #1 is to determine whether blue-enriched light produces a larger phase advance than white light. Specific Aim #2 is to assess the relative contributions of afternoon melatonin and morning bright blue-enriched light to phase advances, and to determine whether there is any merit to a melatonin-only treatment that does not require a light box. Specific Aim #3 is to determine whether distributing the same total duration of bright blue-enriched light into different patterns, by changing the duration of the pulses and their number, can increase the phase advance. Specific Aim #4 is to determine whether the duration of bright light exposure can be reduced while still producing acceptable magnitudes of phase shift. In all studies, circadian phase will be assessed from complete melatonin profiles collected in dim light. We will also measure sleep (with wrist activity monitors and logs), sleepiness and other symptoms (questionnaires) and performance (computerized). These studies will yield practical recommendations for phase shifting the circadian clock and may also provide information about how the human circadian clock responds to light.