Amplitude reduction and phase shifts of melatonin, cortisol and other circadian rhythms after a gradual advance of sleep and light exposure in humans.

BACKGROUND: The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleep-wake cycle has not been fully characterized. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity 'room' light (∼90-150 lux) or moderate light supplemented with bright light (∼10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54% (17-94%) and after bright light by 52% (range 12-84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness. CONCLUSIONS/SIGNIFICANCE: Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift-work, jet-lag and exposure to artificial light.

Temporal dynamics of late-night photic stimulation of the human circadian timing system.

The light-dark cycle is the primary synchronizing factor that keeps the internal circadian pacemaker appropriately aligned with the environmental 24-h day. Although it is known that ocular light exposure can effectively shift the human circadian pacemaker and do so in an intensity-dependent manner, the curve that describes the relationship between light intensity and pacemaker response has not been fully characterized for light exposure in the late biological night. We exposed subjects to 3 consecutive days of 5 h of experimental light, centered 1.5 h after the timing of the fitted minimum of core body temperature, and show that such light can phase advance shift the human circadian pacemaker in an intensity-dependent manner, with a logistic model best describing the relationship between light intensity and phase shift. A similar sigmoidal relationship is also observed between light intensity and the suppression of plasma melatonin concentrations that occurs during the experimental light exposure. As with a simpler, 1-day light exposure during the early biological night, our data indicate that the human circadian pacemaker is highly sensitive even to typical room light intensities during the late biological night, with approximately 100 lux evoking half of the effects observed with light 10 times as bright.