MELATONIN AS A CHRONOBIOTIC - TREATMENT OF CIRCADIAN DESYNCHRONY IN NIGHT WORKERS AND THE BLIND

Although the causes are different, totally blind people (without Light perception) and night shift workers have in common recurrent bouts of insomnia and wake-time sleepiness that occur when their preferred (or mandated) sleep and wake times are out of synchrony with their endoge nous circadian rhythms. In this article, the patterns of circadian des ynchrony in these two populations are briefly reviewed with special em phasis on longitudinal studies in individual subjects that used the ti ming of melatonin secretion as a circadian marker. In totally blind pe ople, the most commonly observed pattern is a free-running rhythm with a stable non-24-h circadian period (24.2-24.5 h), although some subje ctively blind people are normally entrained, perhaps by residually int act retinoypothalamic photic pathways. Experiments at the cellular and behavioral levels have shown that melatonin can produce time dependen t circadian phase shifts. With this in mind, melatonin has been admini stered to blind people in an attempt to entrain abnormal circadian rhy thms, and substantial phase shifts have been accomplished; however, it remains to be demonstrated unequivocally that normal long-term entrai nment can be produced. In untreated night shift workers, the degree an d direction of phase shifting in response to an inverted sleep-wake sc hedule appears to be quite variable. When given at the optimal circadi an time, melatonin treatment appears to facilitate phase shifting in t he desired direction. Melatonin given prior to a night worker's daytim e sleep also may attenuate interference from the circadian alerting pr ocess. Because melatonin has both phase-shifting and sleep-promoting a ctions, night shift workers, who number in the millions, may be the mo st likely group to benefit from treatment.