URINARY 6-SULFATOXYMELATONIN CYCLE-TO-CYCLE VARIABILITY

For either clinical or research purposes, the timing of the nocturnal onset in production of the urinary melatonin metabolite 6-sulfatoxymel atonin (UaMT6s-onset), has been proposed as a reliable and robust mark er of circadian phase. However, given that most circadian rhythms show cycle-to-cycle variability, the statistical reliability of phase esti mates obtained from a single study using UaMT6s-onset remains to be de termined. Following 2 weeks of sleep diary and wrist actigraphy, 15 yo ung, healthy good sleepers participated in four UaMT6s sampling sessio ns spaced 1 day apart. During the sampling sessions subjects remained indoors under low light conditions and hourly urine samples were colle cted from 19:00 to 02:00 h. Samples were subsequently assayed for UaMT 6s using standard radioimmunographic techniques. UaMT6s-onset was dete rmined by the time at which melatonin production exceeded the average of three proceeding trials by 100%. Sleep onset times were derived fro m sleep diary and actigraphic measures taken before the melatonin coll ection nights. We found that there was no significant variation betwee n nights in group mean UaMT6s-onset times, and intraindividual variabi lity was small. In addition, UaMT6s-onset times were highly and signif icantly correlated between nights (grand mean r = 0.804). Our results suggest that within 95% confidence interval limits, individual UaMT6s- onset estimates obtained from a single night UaMT6s-onset study can be used to predict subsequent UaMT6s-onset times within +/-97 min. A clo se temporal relationship was also found between the timing of UaMT6s-o nset and sleep onset. Overall, our results suggest that under entraine d conditions single-session UaMT6s-onset studies can provide reliable individual UaMT6s-onset phase estimates and that the protocol describe d in this study is a practical and noninvasive methodology.