Timing of sleep and its relationship with the endogenous melatonin rhythm

Abstract

While much research has investigated the effects of exogenous melatonin on sleep, less is known about the relationship between the timing of the endogenous melatonin rhythm and the sleep-wake cycle. Significant inter-individual variability in the phase relationship between sleep and melatonin rhythms has been reported although the extent to which the variability reflects intrinsic and/or environmental differences is unknown. We examined the effects of different sleeping schedules on the time of dim light melatonin onset (DLMO) in 28 young, healthy adults. Participants chose to maintain either an early (22:30-06:30 h) or a late (00:30-08:30 h) sleep schedule for at least 3 weeks prior to an overnight laboratory visit. Saliva samples were collected under dim light (<2 lux) and controlled posture conditions to determine salivary DLMO. The 2-h difference between groups in the enforced sleep-wake schedule was associated with a concomitant 1.75-h delay in DLMO. The mean phase relationship between sleep onset and DLMO remained constant (~2 h). The variance in DLMO time, however, was greater in the late group (range 4.5 h) compared to the early group (range 2.4 h) perhaps due to greater effect of environmental influences in delayed sleep types or greater intrinsic instability in their circadian system. The findings contribute to our understanding of individual differences in the human circadian clock and have important implications for the diagnosis and treatment of circadian rhythm sleep disorders, in particular if a greater normative range for phase angle of entrainment occurs in individuals with later sleep-wake schedules.

Keywords: DLMO; circadian rhythm; diurnal preference; melatonin rhythm; phase angle; sleep.

Figure 1

Protocol for the laboratory phase of the study for the early sleepers and late sleepers. Saliva samples (closed circles) began 5.5 h before scheduled pre-laboratory bedtime (dashed line) and continued until 5 h after scheduled bedtime for each group. Ambient light levels were maintained at <2 lux during the saliva sampling period (gray bars) and participants remained awake in a controlled posture. Black bars illustrate the 3-h sleep period permitted after collection of the final saliva sample, as part of the larger protocol.

Figure 2

(A) Individual participants’ melatonin onset (circles) during the first night in the laboratory for the early (n = 11) and late (n = 17) sleep groups. Triangles represent the mean melatonin onset time for each group. Horizontal bars represent the mean sleep period recorded for each group during the final 9 days of the pre-laboratory period. (B) Timing of melatonin onset (circles) relative to scheduled sleep onset (dashed line) (phase angle of entrainment) for each participant in the early (n = 11) and late (n = 17) sleep groups. Triangles represent the mean melatonin onset time for each group.