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.

Evaluation of the Actillume wrist actigraphy monitor in the detection of sleeping and waking.

This study evaluated the Actillume instrument and the modified Action 3 sleep-wake scoring algorithm, in which the scoring factor (P) was set at 0.10, 0.14, 0.20, 0.30, 0.40 and 0.50. Fifteen subjects, each of whom underwent polysomnography with simultaneous wrist actigraphy four times, yielded a total of 60 sleep studies. The sleep data from each subject were divided into four groups. In the high sleep efficiency index groups of the calibration and validation samples, the accuracy of the algorithm significantly differed within six P-values and was highest at P=0.14. In the low sleep efficiency index groups of both samples, however, there were no significant differences in the accuracy. Thus, these results indicate that P=0.14 should be most appropriate for this actigraph and algorithm.

A comparison of sleep detection by wrist actigraphy, behavioral response, and polysomnography.

Two alternative methods for detecting sleep, wrist actigraphy (ACT) and behavioral response monitoring (BRM), were compared to polysomnography (PSG). In the BRM paradigm, a threshold intensity visual or auditory stimulus generated by a palm-top computer was presented about once per minute, and subjects pressed a microswitch if the stimulus was detected. A response within 5 seconds of the stimulus was scored as "wake" and a failure to respond as "sleep." Four males and four females underwent two nights of simultaneous in-home PSG, BRM, and ACT. Each night, subjects underwent a protocol designed to generate five sleep latency trials. Subjects were awakened by alarm clocks at approximately 1-hour intervals and remained awake for 10 minutes before returning to bed for another sleep onset latency (SOL) trial. Minute-by-minute comparisons were made for PSG versus ACT and BRM. All measures were fairly sensitive in detecting sleep, but BRM was more accurate in determining SOL and subsequent wakefulness. Behavioral response monitoring using a tone resulted in more responses and arousals prior to and during light stages of sleep than BRM using a light. It is concluded that BRM has some important advantages as a simple, minimally invasive method for monitoring sleep.

The amplitude of endogenous melatonin production is not affected by melatonin treatment in humans.

A physiological dose of melatonin (0.5 mg) or placebo was given at bedtime to night shift workers (n = 21) for seven days, and endogenous melatonin profiles were measured on the eighth day. The amplitude of endogenous melatonin secretion was unchanged by treatment. Also, a melatonin treatment trial using a 50 mg daily bedtime dose for 37 days to a blind subject resulted in no change in the endogenous melatonin profile. We conclude that circulating melatonin can shift the phase, but does not alter the amplitude, of pineal melatonin secretion.

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.

Melatonin rhythms in night shift workers.

For some time, it has remained uncertain whether the circadian rhythms of permanent night shift workers are adapted to their night-active schedule. Previous studies of this question have often been limited by "masking" (evoked) effects of sleep and activity on body temperature and cortisol, used as marker rhythms. In this study, the problem of masking was minimized by measuring the timing of melatonin production under dim light conditions. Nine permanent night shift workers were admitted to the Clinical Research Center (CRC) directly from their last work shift of the week and remained in dim light while blood samples were obtained hourly for 24 hours. Melatonin concentrations were measured in these samples using a gas-chromatographic mass-spectrometric method. Sleep diaries were completed for two weeks prior to the admission to the CRC. Overall, the onset of the melatonin rhythm was about 7.2 hours earlier (or 16.8 hours later) in the night workers compared to day-active controls. It was not possible to know whether the phase of the melatonin rhythm was the result of advances or delays. In night shift workers, sleep was initiated (on average) about three hours prior to the onset of melatonin production. In contrast, day-active subjects initiated sleep (on average) about three hours after their melatonin onset. Thus, the sleep times selected by night shift workers may not be well-synchronized to their melatonin rhythm, assumed to mark the phase of their underlying circadian pacemaker.

Circadian rhythm abnormalities in totally blind people: incidence and clinical significance.

When people are completely isolated from environmental time cues, their circadian rhythms free run with a nearly 24-h cycle, generated by an internal body clock. Free-running temperature, cortisol, and melatonin rhythms have also been described in totally blind people, even though they were living in normal society and had access to abundant time cues; thus an intact visual system may be essential for synchronization of the circadian system. However, because of the small numbers of subjects studied, the incidence and clinical significance of circadian rhythm abnormalities among the blind has remained uncertain. In this study, plasma melatonin (n = 20), cortisol (n = 4), and sleep propensity (n = 1) were measured in serial samples taken from totally blind subjects for 24 h. Most totally blind subjects had circadian rhythm abnormalities. In about half of the subjects, the rhythms were free-running. Some blind subjects suffered recurrent insomnia and daytime sleepiness that were maximal when the internal rhythms were out of phase with the preferred sleep times. The high incidence of abnormal circadian rhythms in blind people underscores the importance of the light-dark cycle as an important environmental synchronizer for the human circadian system.

Melatonin administration to blind people: phase advances and entrainment.

The purpose of this study was to test the phase-shifting and entraining effects of melatonin in human subjects. Five totally blind men were found in a previous study to have free-running endogenous melatonin rhythms. Their rhythms were remarkably stable, so that any deviation from the predicted phase was readily detectable. After determination of their free-running period and phase, they were given exogenous melatonin (5 mg) at bedtime (2200 hr) for 3 weeks, in a double-blind, placebo-controlled trial. The effects on the endogenous melatonin rhythm were assessed at intervals ranging from several days to 2 weeks. Exogenous administration of melatonin phase-advanced their endogenous melatonin rhythms. In three of the subjects, cortisol was shown to be phase-shifted in tandem with the melatonin rhythm. A sixth subject [one of the coauthors (JS)] was previously found to have free-running cortisol and temperature rhythms and was plagued by recurrent insomnia and daytime sleepiness. He had tried unsuccessfully to entrain his rhythms for over 10 years. After he took melatonin (7 mg at 2100 hr), his insomnia and sleepiness resolved. Determination of his endogenous melatonin rhythm after about a year of treatment demonstrated endogenous rhythms that appeared normally entrained. The treatment of blind people with free-running rhythms has many advantages for demonstrating chronobiological effects of hormones or drugs.

Is winter depression a bipolar disorder?

Sixty-one winter depressive patients were evaluated for evidence of bipolar illness. Using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version and the General Behavior Inventory, only nine (15%) could be considered bipolar. On prospective evaluation of patients during the summer following winter depression, few showed signs of manic or hypomanic symptoms. Also, few patients had a family history of bipolar illness. When patients were asked to evaluate symptoms of winter depression, lack of energy was found to be the most prominent feature of the syndrome.