Is Sleep per se a Zeitgeber in Humans?

Abstract

It is not clear whether shifting of sleep per se, without a concomitant change in the light-dark cycle, can induce a phase shift of the human circadian pacemaker. Two 9-day protocols (crossover, counterbalanced order) were completed by 4 men and 6 women (20-34 years) after adherence to a 2330 to 0800 h sleep episode at home for 2 weeks. Following a modified baseline constant routine (CR) protocol on day 2, they remained under continuous near-darkness (< 0.2 lux, including sleep) for 6 days. Four isocaloric meals were equally distributed during scheduled wakefulness, and their timing was held constant. Subjects remained supine inbed from 2100 to 0800 h on all days; sleep was fixed from 2330 to 0800 h in the control condition and was gradually advanced 20 min per day during the sleep advance condition until a 2-h difference had been attained. On day 9, a 25 to 27 h CR protocol (approximately 0.1 lux) was carried out. Phase markers were the evening decline time of the core body temperature (CBT) rhythm and salivary melatonin onset (3 pg/ml threshhold). In the fixed sleep condition, the phase drift over 7 days ranged from +1.62 to -2.56 h (for both CBT and melatonin rhythms, which drifted in parallel). The drifts were consistently advanced in the sleep advance schedule by +0.66 +/- 0.23 (SEM) h for CBT (p = 0.02) and by 0.27 +/- 0.14 h for melatonin rhythms (p = 0.09). However, this advance was small to medium according to effect size. Sleep per se may feed back onto the circadian pacemaker, but it appears to be a weak zeitgeber in humans.

An arousing, musically enhanced bird song stimulus mediates circadian rhythm phase advances in dim light

“…The direction and magnitude of DLMO and CBT minimum phase shifts also were positively related, demonstrating a direct effect on the circadian timing system, similar to other studies (8,18,20,23,30,39,58). DLMO occurred a little over 7 h before CBT minimum, at baseline and after exposure, with a positive relationship between the two markers, as has been reported previously (7,9,14,23).…”

“…Notably, one study failed to detect dilation at decibel levels comparable with that used in this study (53). To investigate this question further, subsequent studies could examine the effects of musically enhanced bird song in subjects maintained under conditions of near darkness (6,20) or in the totally blind (42), as has been done for other nonphotic stimuli, or could test subjects in the paradigm used by Cajochen et al (16).…”

Addition of a non-photic component to a light-based mathematical model of the human circadian pacemaker

“…Furthermore, the magnitude of the effect of non-photic stimuli observed in Model PNP predictions is small enough that it could be (a) masked by the stronger effects of light in that and other studies, (b) lost in the variability of circadian phase markers due to sensitivity of the assays, or (c) confounded by the natural drift in the pacemaker as well as background light levels. Other studies have reported that timing of sleep (Danilenko et al, 2003) may have an effect on the circadian pacemaker, independent of light. Furthermore, our theoretical non-photic PRC generated by Model PNP has a similar shape as compared to other non-photic PRCs observed in humans in response to exercise and exogenous melatonin, findings which indicate that there is a 12-h anti-phase relationship to the light PRC.…”

“…One study of a forced 24-h sleep-wake schedule in dim light (~5 lux) suggests that the imposed rest-activity cycle may be sufficient to entrain the pacemaker of some subjects to the 24-h day (Nakamura, 1996). In a more recent experiment, subjects scheduled to a protocol that advanced the sleep-wake schedule by less than one hour each day (T = ~23.67 h) in <0.2 lux phase advanced towards the entraining stimuli compared to control subjects in the same lighting condition scheduled to a T = 24.0-h protocol (Danilenko et al, 2003). In studies that examined the effect of sleep deprivation on the circadian pacemaker, it has been reported that a 40-h sleep deprivation in dim light (between ~1.5 and 13 lux) induced, on average, a phase delay shift Wright et al 2005) that was larger than that which could be explained by the drift due to intrinsic period of the circadian pacemaker .…”

Sleep and Emotional Functions

“…Even a minimal misalignment between circadian phase and sleep phase can deteriorate mood (Danilenko et al 2003), which may also in part explain mood-related problems (e.g., irritability) in jet-lag (Waterhouse et al 2005), and severity of unipolar depression (Hasler et al 2010). Stress can also disrupt the circadian cycle (Meerlo et al 2002), leading to depressive episodes in vulnerable individuals (Ehlers et al 1988).…”