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

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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.