Intrinsic Period and Light Intensity Determine the Phase Relationship between Melatonin and Sleep in Humans

Abstract

The internal circadian clock and sleep-wake homeostasis regulate the timing of human brain function, physiology, and behavior so that wakefulness and its associated functions are optimal during the solar day and that sleep and its related functions are optimal at night. The maintenance of a normal phase relationship between the internal circadian clock, sleep-wake homeostasis, and the light-dark cycle is crucial for optimal neurobehavioral and physiological function. Here, the authors show that the phase relationship between these factors-the phase angle of entrainment (psi)-is strongly determined by the intrinsic period (tau) of the master circadian clock and the strength of the circadian synchronizer. Melatonin was used as a marker of internal biological time, and circadian period was estimated during a forced desynchrony protocol. The authors observed relationships between the phase angle of entrainment and intrinsic period after exposure to scheduled habitual wakefulness-sleep light-dark cycle conditions inside and outside of the laboratory. Individuals with shorter circadian periods initiated sleep and awakened at a later biological time than did individuals with longer circadian periods. The authors also observed that light exposure history influenced the phase angle of entrainment such that phase angle was shorter following exposure to a moderate bright light (approximately 450 lux)-dark/wakefulness-sleep schedule for 5 days than exposure to the equivalent of an indoor daytime light (approximately 150 lux)-dark/wakefulness-sleep schedule for 2 days. These findings demonstrate that neurobiological and environmental factors interact to regulate the phase angle of entrainment in humans. This finding has important implications for understanding physiological organization by the brain's master circadian clock and may have implications for understanding mechanisms underlying circadian sleep disorders.

Entrainment of the human circadian pacemaker to longer-than-24-h days

“…Note that both MEL on and MEL off phases were slightly delayed on CR3 compared with D2, D3, and CR1 (ANOVA, Student-Newman-Keuls, P Ͻ 0.0001). This change, which likely occurred in response to the phasedelaying effect of 5 days in 450 lux, is consistent with previous finding in animals (9,13) and humans (23), showing that the phase angle narrows with increased light intensities.…”

“…3 reveals that the phase angle of entrainment, as determined by the relationship between MEL on and habitual bedtime ( MELon ), is strongly correlated with such that participants with shorter circadian periods have an earlier MELon than those with longer periods. This is consistent with correlations from temperature data collected immediately after entrainment to a 24-h day (22) and even after entrainment to a variety of daylength and lighting conditions (23). The very high correlation demonstrated in Fig.…”

“…As shown both in nonhuman species (13,25) and humans (22,23), the phase angle of entrainment between the imposed T-cycle and the phase marker of an entrained rhythm is a function of the difference in their period [ ϭ f(T Ϫ )] and of the strength of the zeitgeber. Phase angle widens as T differs from , and narrows as zeitgeber strength increases (13).…”

Decreased sensitivity to phase-delaying effects of moderate intensity light in older subjects

“…Because of these influences on sleep, age-related changes in the circadian timing system have been hypothesized to contribute to the observed age-related changes in sleep. The circadian system in humans has an average period (cycle length) that is longer than 24 h [15;18;34;61], and is entrained (synchronized) to the 24 h day by regular exposure to light and darkness [60]. Light has a phase-dependent effect on the circadian system [21], with light exposure during the late subjective day/early subjective night causing phase delay shifts (to a later hour), light during the late subjective night/early subjective day causing phase advance shifts (to an earlier hour), and light exposure during the subjective daytime causing very small phase shifts [35;39;47].…”

The Electrification–Malaria Nexus: The Case of Rural Uganda

“…Winther, 2011). Also larger social events -such as sport activities -can now be practised outdoors in the evening thanks to artificial lighting and a major impact of electrification is to alter the 'light and day input' through controlling artificial light during solar darkness (Wright et al, 2005;Louzada et al, 2004). In fact, some authors have already argued that increased time spent outside the house during evening and night hours might have caused an increase in malaria infection based on evidence from the 2 Many communities living in rural areas where malaria is endemic use aromatic smokes in addition to wood fuel, i.e.…”