Mary L. Blood

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.

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

Matsumoto M, Sack RL, Blood ML, Lewy AJ. The amplitude of endogenous melatonin production is not affected by melatonin treatment in humans. J. Pineal Res. 1997; 22:42–44.

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

Abstract 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 significandy 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.

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.

The Influence of Melatonin on the Human Circadian Clock

Now that it has been established that experimental administration of melatonin has circadian phase-shifting effects in humans, we can speculate about its endogenous function. More specifically, melatonin in physiologic amounts can produce effects that are described by a phase response curve (PRC) (Lewy et al., 1990a; Lewy et al., 1992; Lewy et al., 1991; Lewy et al., 1990b; Lewy et al., 1991; Zaidan et al., 1994) that is about 12 hours out of phase with the PRCs to light (Czeisler et al., 1989; Honma and Honma, 1988; Minors et al., 1991; Wever, 1989). Therefore, it appears that the most likely role of endogenous melatonin production in humans is to augment phase-shifting and entrainment of the endogenous circadian pacemaker (ECP) by the light-dark cycle. This is accomplished through the suppressant effect of light on melatonin production (Lewy et al., 1980).