Charmane I. Eastman

Light Treatment for Sleep Disorders: Consensus Report VI. Shift Work

The unhealthy symptoms and many deleterious consequences of shift work can be explained by a mismatch between the work-sleep schedule and the internal circadian rhythms. This mismatch occurs because the 24-h zeitgebers, such as the natural light-dark cycle, keep the circadian rhythms from phase shifting to align with the night-work, day-sleep schedule. This is a review of studies in which the sleep schedule is shifted several hours, as in shift work, and bright light is used to try to phase shift circadian rhythms. Phase shifts can be produced in laboratory studies, when subjects are kept indoors, and faster phase shifting occurs with appropriately timed bright light than with ordinary indoor (dim) light. Bright light field studies, in which subjects live at home, show that the use of artificial nocturnal bright light combined with enforced daytime dark (sleep) periods can phase shift circadian rhythms despite exposure to the conflicting 24-h zeitgebers. So far, the only studies on the use of bright light for real shift workers have been conducted at National Aeronautics and Space Administration (NASA). In general, the bright light studies support the idea that the control of light and dark can be used to overcome many of the problems of shift work. However, despite ongoing practical applications (such as at NASA), much basic research is still needed.

The effects of prior light history on the suppression of melatonin by light in humans

Abstract: We investigated the impact of light exposure history on light sensitivity in humans, as assessed by the magnitude of the suppression of melatonin secretion by nocturnal light. The hypothesis was that following a week of increased daytime bright‐light exposure, subjects would become less sensitive to light, and that after a week of restriction to dimmer light they would become more sensitive. During the bright week, subjects (n = 12) obtained 4.3 ± 0.4 hr of bright light per day (by going outside and using light boxes indoors). During the dim week, they wore dark goggles (about 2% light transmission) when outside during daylight and spent 1.4 ± 0.9 hr per day outside. Saliva samples were obtained every 30 min for 7 hr in dim light (<15 lux) on two consecutive nights (baseline and test night) at the end of each week. On the test night, 500 lux was presented for 3 hr in the middle of the collection period to suppress melatonin. There was significantly more suppression after the dim week compared with after the bright week (to 53 versus 41% of the baseline night values, P < 0.05). However, there were large individual differences, and the difference between the bright and dim weeks was most pronounced in seven of the 12 subjects. Possible reasons for these individual differences are discussed, including the possibility that 1 wk was not long enough to change light sensitivity in some subjects. In conclusion, this study suggests that the circadian systems sensitivity to light can be affected by a recent change in light history.

Combinations of Bright Light, Scheduled Dark, Sunglasses, and Melatonin to Facilitate Circadian Entrainment to Night Shift Work

Various combinations of interventions were used to phase-delay circadian rhythms to correct their misalignment with night work and day sleep. Young participants (median age = 22, n= 67) participated in 5 consecutive simulated night shifts (2300 to 0700) and then slept at home (0830 to 1530) in darkened bedrooms. Participants wore sunglasses with normal or dark lenses (transmission 15% or 2%) when outside during the day. Participants took placebo or melatonin (1.8 mg sustained release) before daytime sleep. During the night shifts, participants were exposed to a moving (delaying) pattern of intermittent bright light (~5000 lux, 20 min on, 40 min off, 4-5 light pulses/night) or remained in dimlight (~150 lux). There were 6 intervention groups ranging fromthe least complex (normal sunglasses) to the most complex (dark sunglasses + bright light + melatonin). The dim light melatonin onset (DLMO) was assessed before and after the night shifts (baseline and final), and 7 h was added to estimate the temperature minimum (Tmin). Participants were categorized by their amount of reentrainment based on their final Tmin: not re-entrained (Tmin before the daytime dark/sleep period), partially re-entrained (Tmin during the first half of dark/sleep), or completely re-entrained (Tmin during the second half of dark/ sleep). The sample was split into earlier participants (baseline Tmin = 0700, sunlight during the commute home fell after the Tmin) and later participants (baseline Tmin > 0700). The later participants were completely re-entrained regardless of intervention group, whereas the degree of re-entrainment for the earlier participants depended on the interventions. With bright light during the night shift, almost all of the earlier participants achieved complete re-entrainment, and the phase delay shift was so large that darker sunglasses and melatonin could not increase its magnitude. With only room light during the night shift, darker sunglasses helped earlier participants phase-delay more than normal sunglasses, but melatonin did not increase the phase delay. The authors recommendthecombination of intermittent bright light during the night shift, sunglasses (as dark as possible) during the commute home, and a regular, early daytime dark/sleep period if the goal is complete circadian adaptation to night-shift work.

Suprachiasmatic nuclei lesions eliminate circadian temperature and sleep rhythms in the rat

We conducted a long-term study of the circadian rhythms of temperature and sleep in the rat after lesions of the suprachiasmatic nuclei (SCN). Brain temperature was measured with thermistors and sleep-wake was scored on the basis of continuously recorded EEG using a computerized system. Rats with complete SCN lesions did not exhibit circadian rhythms in constant dim illumination. Rats with partial SCN lesions generated weak and variable free-running rhythms, and when exposed to a light-dark cycle, some showed a reduced amplitude and altered waveform relative to normal rats. A few rats with partial SCN lesions showed a recovery of function. There was little difference between the circadian rhythms in temperature and waking, and these measures responded similarly to all lesions. Thus, no support was found for the notions that anatomically distinct oscillators control the circadian rhythms of temperature and activity, or that an oscillator outside of the SCN controls the circadian rhythm of temperature.

How to use light and dark to produce circadian adaptation to night shift work

The circadian rhythms of night shift workers do not usually adjust to their unusual work and sleep schedules, reducing their quality of life and producing potentially dangerous health and safety problems. This paper reviews field studies of simulated night work in which shifted light-dark cycles were constructed with artificial bright or medium-intensity light to produce circadian adaptation, ie the shifting of circadian rhythms to align with night work and day sleep schedules. By using these studies we describe fundamental principles of human circadian rhythms relevant to producing circadian adaptation to night shift work at a level designed for the reader with only a basic knowledge of circadian rhythms. These principles should enable the reader to start designing work/sleep-light/dark schedules for producing circadian adaptation in night shift workers. One specific schedule is presented as an example. Finally, we discuss phase-response curves to light and clarify common misconceptions about the production of circadian rhythm phase shifts.

How to Trick Mother Nature into Letting You Fly Around or Stay Up All Night

Night shift work and rapid transmeridian travel result in a misalignment between circadian rhythms and the new times for sleep, wake, and work, which has health and safety implications for both the individual involved and the general public. Entrainment to the new sleep/wake schedule requires circadian rhythms to be phase-shifted, but this is often slow or impeded. The authors show superimposed light and melatonin PRCs to explain how to appropriately time these zeitgebers to promote circadian adaptation. They review studies in which bright light and melatonin were administered to try to counteract jet lag or to produce circadian adaptation to night work. They demonstrate how jet lag could be prevented entirely if rhythms are shifted before the flight using their preflight plan and discuss the combination of interventions that they now recommend for night shift workers.

Circadian temperature and wake rhythms of rats exposed to prolonged continuous illumination

The purpose of this study was to simultaneously measure temperature and sleep in the rat under continuous illumination in an attempt to reveal properties of the underlying circadian oscillators. At first, the circadian rhythms of temperature and wake free-ran in parallel. Within weeks or months, circadian arrhythmicity developed in most animals. Both circadian rhythms eventually damped out, even at fairly low light intensities. The circadian rhythm of wake was weaker and disintegrated sooner than the circadian rhythm of temperature. Although the data did not rule out control by separate circadian oscillators, one for temperature and one for wake, a single oscillator model was sufficient to explain this phenomenon. Ultradian variations with a period of about 2-5 hr were superimposed upon the circadian rhythms. When the circadian rhythms damped out, the ultradian variations remained. The ultradian bursts of wake preceded the ultradian bursts of temperature, suggesting a causal relationship. On the other hand, the circadian rhythm of temperature could not be dependent on the circadian rhythm of wakefulness, because the temperature rhythm could persist while the wake rhythm was absent.

Preflight Adjustment to Eastward Travel: 3 Days of Advancing Sleep with and without Morning Bright Light

Jet lag is caused by a misalignment between circadian rhythms and local destination time. As humans typically take longer to re-entrain after a phase advance than a phase delay, eastward travel is often more difficult than westward travel. Previous strategies to reduce jet lag have focused on shaping the perceived light-dark cycle after arrival, in order to facilitate a phase shift in the appropriate direction. Here we tested treatments that travelers could use to phase advance their circadian rhythms prior to eastward flight. Thus, travelers would arrive with their circadian rhythms already partially re-entrained to local time. We determined how far the circadian rhythms phase advanced, and the associated side effects related to sleep and mood. Twenty-eight healthy young subjects participated in 1 of 3 different treatments, which all phase advanced each subjects habitual sleep schedule by 1 h/day for 3 days. The 3 treatments differed in morning light exposure for the 1st 3.5 h after waking on each of the 3 days: continuous bright light (> 3000 lux), intermittent bright light (> 3000 lux, 0.5 h on, 0.5 off, etc.), or ordinary dim indoor light (< 60 lux). A phase assessment in dim light (< 10 lux) was conducted before and after the treatments to determine the endogenous salivary dim light melatonin onset (DLMO). The mean DLMO phase advances in the dim, intermittent, and continuous light groups were 0.6, 1.5, and 2.1 h, respectively. The intermittent and continuous light groups advanced significantly more than the dim light group (p < 0.01) but were not significantly different from each other. The side effects as assessed with actigraphy and logs were small. A 2-h phase advance may seem small compared to a 6- to 9-h time zone change, as occurs with eastward travel from the USA to Europe. However, a small phase advance will not only reduce the degree of re-entrainment required after arrival, but may also increase postflight exposure to phase-advancing light relative to phase-delaying light, thereby reducing the risk of antidromic re-entrainment. More days of preflight treatment could be used to produce even larger phase advances and potentially eliminate jet lag.

Effects of melatonin administration on daytime sleep after simulated night shift work

Disturbed sleep and on‐the‐job sleepiness are widespread problems among night shift workers. The pineal hormone melatonin may prove to be a useful treatment because it has both sleep‐promoting and circadian phase‐shifting effects. This study was designed to isolate melatonin’s sleep‐promoting effects, and to determine whether melatonin could improve daytime sleep and thus improve night time alertness and performance during the night shift. The study utilized a placebo‐controlled, double‐blind, cross‐over design. Subjects (n=21, mean age=27.0 ± 5.0 years) participated in two 6‐day laboratory sessions. Each session included one adaptation night, two baseline nights, two consecutive 8‐h night shifts followed by 8‐h daytime sleep episodes and one recovery night. Subjects took 1.8 mg sustained‐release melatonin 0.5 h before the two daytime sleep episodes during one session, and placebo before the daytime sleep episodes during the other session. Sleep was recorded using polysomnography. Sleepiness, performance, and mood during the night shifts were evaluated using the multiple sleep latency test (MSLT) and a computerized neurobehavioral testing battery. Melatonin prevented the decrease in sleep time during daytime sleep relative to baseline, but only on the first day of melatonin administration. Melatonin increased sleep time more in subjects who demonstrated difficulty in sleeping during the day. Melatonin had no effect on alertness on the MSLT, or performance and mood during the night shift. There were no hangover effects from melatonin administration. These findings suggest that although melatonin can help night workers obtain more sleep during the day, they are still likely to face difficulties working at night because of circadian rhythm misalignment. The possibility of tolerance to the sleep‐promoting effects of melatonin across more than 1 day needs further investigation.

Sleep logs of young adults with self-selected sleep times predict the dim light melatonin onset.

The purpose of this study was to determine whether a sleep log parameter could be used to estimate the circadian phase of normal, healthy, young adults who sleep at their normal times, and thus naturally have day-to-day variability in their times of sleep. Thus, we did not impose any restrictions on the sleep schedules of our subjects (n=26). For 14 d, they completed daily sleep logs that were verified with wrist activity monitors. On day 14, salivary melatonin was sampled every 30 min in dim light from 19:00 to 07:30h to determine the dim light melatonin onset (DLMO). Daily sleep parameters (onset, midpoint, and wake) were taken from sleep logs and averaged over the last 5, 7, and 14 d before determination of the DLMO. The mean DLMO was 22:48±01:30 h. Sleep onset and wake time averaged over the last 5 d were 01:44±01:41 and 08:44±01:26 h, respectively. The DLMO was significantly correlated with sleep onset, midpoint, and wake time, but was most strongly correlated with the mean midpoint of sleep from the last 5 d (r=0.89). The DLMO predicted using the mean midpoint of sleep from the last 5 d was within 1 h of the DLMO determined from salivary melatonin for 92% of the subjects; in no case did the difference exceed 1.5 h. The correlation between the DLMO and the score on the morningness–eveningness questionnaire was significant but comparatively weak (r=−0.48). We conclude that the circadian phase of normal, healthy day-active young adults can be accurately predicted using sleep times recorded on sleep logs (and verified by actigraphy), even when the sleep schedules are irregular.