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

在许多情况下，现代人发现他们的昼夜节律与 他们所期望的睡眠/觉醒时间表，例如在喷气式飞机旅行后，轮班工作期间，以及在某些睡眠障碍中 比如睡眠期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， 胃肠道不适并最终导致健康问题。明亮的光线和褪黑激素已经被用来帮助 相位移动人体生物钟，但很少有人做测试的组合。近期精彩 一些发现表明，昼夜节律系统使用一种新的光感受器（除了视杆细胞和视锥细胞之外）， 对短波长（蓝色）光最敏感，并且蓝光可以产生较大的相移 而不是其他波长。 我们将在一个实用的方案中测试蓝色富集光和褪黑激素的组合， 日常使用在家里和工作。在所有研究中，睡眠时间表将逐渐提前， 在大多数研究中，小剂量的褪黑激素将在下午使用，明亮的蓝光（来自一个 单个灯箱）将在早晨使用，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，同时保持昼夜节律一致 以防止副作用或时差综合症。 具体目标#1是确定蓝色富集光是否产生比白色更大的相位超前 光具体目标#2是评估下午褪黑激素和早晨亮蓝的相对贡献。 丰富的光相位的进步，并确定是否有任何优点，以褪黑激素只有治疗 它不需要灯箱。具体目标#3是确定是否分配相同的总持续时间 通过改变脉冲的持续时间和数量， 可以增加相位超前。具体目标#4是确定强光的持续时间 可以减少曝光，同时仍然产生可接受的相位抖动幅度。在所有研究中， 将从在昏暗光线下收集的完整褪黑激素分布图中评估昼夜节律相位。我们还将 测量睡眠（使用手腕活动监测器和日志），嗜睡和其他症状（问卷）， 性能（计算机化）。这些研究将产生实际的建议，相移 生物钟可以是生物钟，并且还可以提供关于人类生物钟如何对光作出响应的信息。

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-enrichedlight (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 orjet-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 stillproducing acceptable magnitudes of phase shin. 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.