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

描述(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想要的睡眠/醒来时间表不一致，例如在飞机旅行后，在轮班工作期间，以及在一些睡眠障碍中，如睡眠相延迟综合症。这种错位会导致过度疲劳、昏昏欲睡、警觉性下降、注意力不集中、表现受损、睡眠时间缩短和睡眠中断、胃肠道不适以及最终的健康问题。强光和褪黑素已经被用来帮助人类生物钟的相移，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对短波长(蓝色)光最敏感的新型光感受器(除了杆状和锥状)，并且蓝色光比其他波长产生更大的相移。我们将测试富蓝光和褪黑素的组合，这是一种适用于家庭和工作中日常使用的方案。在所有的研究中，睡眠时间表将逐渐提前，在大多数研究中，下午将使用小剂量的褪黑素，早上将使用明亮的蓝光(来自单一灯箱)，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尽可能大的相位提前，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类型的症状。具体目标#1是确定富蓝光是否比白光产生更大的相位推进。具体目标#2是评估下午褪黑素和早晨明亮的蓝光对相位推进的相对贡献，并确定不需要灯箱的仅使用褪黑素的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目，将相同的总持续时间的明亮的富蓝光分布到不同的图案中，是否可以增加相位推进。具体目标#4是确定是否可以减少强光曝光的持续时间，同时仍能产生可接受的相移幅度。在所有的研究中，昼夜节律阶段将根据在昏暗的光线下收集的完整的褪黑素图谱来评估。我们还将测量睡眠(通过手腕活动监测器和日志)、困倦和其他症状(问卷)和表现(计算机化)。这些研究将为生物钟的相移提供实用的建议，并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.