Altered Circadian Rhythm of Melatonin Concentrations in Hypocretin-Deficient Men

Abstract

Hypocretin deficiency causes narcolepsy. It is unknown whether melatonin secretion is affected in this sleep disorder. Therefore, in both narcolepsy patients and matched controls, the authors measured plasma melatonin levels hourly for 24 h before and after 5 days of sodium oxybate (SXB) administration. Although mean melatonin concentrations were similar between patients and controls, in narcoleptics the percentage of 24-h melatonin secreted during the daytime was significantly higher, and melatonin secretion exhibited a weaker coupling to sleep. SXB did not affect melatonin secretion. These findings suggest that hypocretin deficiency might disturb both the circadian control of melatonin release and its temporal association with sleep. (Author correspondence: [email protected])

Keywords:

• Diurnal rhythm
• GHB
• Narcolepsy
• Orexin
• Polysomnography
• Sodium oxybate

ACKNOWLEDGMENTS

This study was supported by UCB pharma. We are greatly indebted to the volunteers who participated in this study. In addition, we would like to thank E. J. M. Ladan-Eygenraam, J. van Vliet-de Regt, C. Calgari, and P. J. van Someren for technical assistance during the study.

Declaration of Interest: This study was supported by UCB pharma. Dr. Lammers has served as a paid member of the UCB advisory board and received lecture fees and conference travel support from UCB pharma. Dr. Lammers also did consultancy for UCB pharma and provided expert testimony for UCB pharma, Jazz pharmaceuticals, and Bioprojet. Dr. Overeem has served as a paid member of the UCB advisory board and received lecture fees from UCB pharma, Novartis, and Boehringer Ingelheim. He also received conference travel support from UCB pharma. Dr. Pévet received grants from l'Institut de recherché Internationales SERVIER, and lecture fees from Eutherapy. C. E. H. M. Donjacour received conference travel support from UCB pharma. The other authors report no financial conflict of interest. For this study we used sodium oxybate (xyrem) from UCB Pharma.