Morning vs evening light treatment of patients with winter depression.

BACKGROUND: According to the phase-shift hypothesis for winter depression, morning light (which causes a circadian phase advance) should be more antidepressant than evening light (which causes a delay). Although no studies have shown evening light to be more antidepressant than morning light, investigations have shown either no difference or morning light to be superior. The present study assesses these light-exposure schedules in both crossover and parallel-group comparisons. METHODS: Fifty-one patients and 49 matched controls were studied for 6 weeks. After a prebaseline assessment and a light/dark and sleep/wake adaptation baseline week, subjects were exposed to bright light at either 6 to 8 AM or 7 to 9 PM for 2 weeks. After a week of withdrawal from light treatment, they were crossed over to the other light schedule. Dim-light melatonin onsets were obtained 7 times during the study to assess circadian phase position. RESULTS: Morning light phase-advanced the dim-light melatonin onset and was more antidepressant than evening light, which phase-delayed it. These findings were statistically significant for both crossover and parallel-group comparisons. Dim-light melatonin onsets were generally delayed in the patients compared with the controls. CONCLUSIONS: These results should help establish the importance of circadian (morning or evening) time of light exposure in the treatment of winter depression. We recommend that bright-light exposure be scheduled immediately on awakening in the treatment of most patients with seasonal affective disorder.

Capturing the circadian rhythms of free-running blind people with 0.5 mg melatonin.

We have recently shown that six of seven totally blind people (who had free-running circadian rhythms with periods longer than 24 h) could be entrained (synchronized) to a nightly dose of 10 mg melatonin. After treatment discontinuation and re-entrainment to the 10 mg dose, we further found in three of these subjects that the dose could be gradually reduced to 0.5 mg without loss of effect. The question then arose: can a de novo (starting) dose of 0.5 mg initially capture free-running rhythms? Following withdrawal of the stepped-down 0.5 mg dose and consequent release into a free-run, the same three individuals were given 0.5 mg of melatonin de novo. All entrained within a few weeks.

Melatonin treatment of winter depression: a pilot study.

Five patients with winter depression received low doses of melatonin in the afternoon, and five patients received placebo capsules. Melatonin treatment significantly decreased depression ratings compared to placebo. If these findings are replicated in a larger sample with documentation of expected phase shifts, the phase shift hypothesis will be substantially supported.

The human phase response curve (PRC) to melatonin is about 12 hours out of phase with the PRC to light.

Melatonin's timekeeping function is undoubtedly related to the fact that it is primarily produced during nighttime darkness; that is, melatonin and light occur at opposite times. The human phase response curve (PRC) to melatonin appears to be about 12h out of phase with the PRC to light. These striking complementarities, together with light's acute suppressant effect on melatonin production, suggest that a function for endogenous melatonin is to augment entrainment of the circadian pacemaker by the light-dark cycle. The melatonin PRC also indicates correct administration times for using exogenous melatonin to treat circadian phase disorders.

Melatonin marks circadian phase position and resets the endogenous circadian pacemaker in humans.

Measuring the dim light melatonin onset (DLMO) is a useful and practical way to assess circadian phase position in humans. As a marker for the phase and period of the endogenous circadian pacemaker, the DLMO has been shown to advance with exposure to bright light in the morning and to delay with exposure to bright light in the evening. This 'phase response curve' (PRC) to light has been applied in the treatment of winter depression, jet lag and shift work, as well as circadian phase sleep disorders. Exogenous melatonin has phase-shifting effects described by a PRC that is about 12 h out of phase with the PRC to light. That is, melatonin administration in the morning causes phase delays and in the afternoon causes phase advances. All of the circadian phase disorders that have been successfully treated with appropriately timed exposure to bright light can be treated with appropriately scheduled melatonin administration. Melatonin administration is more convenient and therefore may be the preferred treatment.