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Melatonin Acutely Improves the Neuroendocrine Architecture of Sleep in Blind Individuals

Departments of Neuroendocrinology (S.F., R.S., M.H., J.B., H.L.F.) and Internal Medicine (R.S., J.B., H.L.F.), University of Lübeck, D-23538 Lübeck, Germany

Address all correspondence and requests for reprints to: Jan Born, University of Lübeck, Department of Neuroendocrinology, Ratzeburger Allee 160, Hs. 23a, D-23538 Lübeck, Germany. E-mail: born{at}kfg.u-luebeck.de.

In blind individuals, the absence of light cues results in disturbances of sleep and sleep-related neuroendocrine patterns. The Zeitgeber influence of light on the timing of sleep is assumed to be mediated by melatonin, a hormone of the pineal gland, whose secretion is inhibited by light and enhanced during darkness. Here, we investigated whether a single administration of melatonin improves sleep and associated neuroendocrine patterns in blind individuals. In a double-blind crossover study, 12 totally blind subjects received 5 mg melatonin and placebo orally 1 h before bedtime starting at 2300 h. The dose used enhanced blood melatonin concentrations to clearly supraphysiological levels. Melatonin increased total sleep time and sleep efficiency (P < 0.05, respectively) and reduced time awake (P < 0.05). The increment in total sleep time was primarily due to an increase in stage 2 sleep (P < 0.01) and a slight increase in rapid eye movement sleep (P < 0.06). Most important, melatonin normalized in parallel the temporal pattern of ACTH and cortisol plasma concentration. While after placebo, ACTH and cortisol levels did not differ between early and late sleep, melatonin induced the typical suppression of pituitary-adrenal activity during early sleep and a distinct rise during late sleep (P < 0.01, respectively). Cortisol nadir values were also decreased after melatonin (P < 0.05). We conclude from these data that in totally blind individuals the single administration of a clearly pharmacological dose of melatonin can improve sleep function by synchronizing in time the inhibition of pituitary-adrenal activity with central nervous sleep processes.

This study was funded by Grant no. 475 from the Deutsche Forschungsgemeinschaft (to J.B.).

Abbreviations: REM, Rapid eye movement; SCN, suprachiasmatic nucleus; SWS, slow wave sleep.