Anne-Marie Chang

Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness

Significance The use of light-emitting electronic devices for reading, communication, and entertainment has greatly increased recently. We found that the use of these devices before bedtime prolongs the time it takes to fall asleep, delays the circadian clock, suppresses levels of the sleep-promoting hormone melatonin, reduces the amount and delays the timing of REM sleep, and reduces alertness the following morning. Use of light-emitting devices immediately before bedtime also increases alertness at that time, which may lead users to delay bedtime at home. Overall, we found that the use of portable light-emitting devices immediately before bedtime has biological effects that may perpetuate sleep deficiency and disrupt circadian rhythms, both of which can have adverse impacts on performance, health, and safety. In the past 50 y, there has been a decline in average sleep duration and quality, with adverse consequences on general health. A representative survey of 1,508 American adults recently revealed that 90% of Americans used some type of electronics at least a few nights per week within 1 h before bedtime. Mounting evidence from countries around the world shows the negative impact of such technology use on sleep. This negative impact on sleep may be due to the short-wavelength–enriched light emitted by these electronic devices, given that artificial-light exposure has been shown experimentally to produce alerting effects, suppress melatonin, and phase-shift the biological clock. A few reports have shown that these devices suppress melatonin levels, but little is known about the effects on circadian phase or the following sleep episode, exposing a substantial gap in our knowledge of how this increasingly popular technology affects sleep. Here we compare the biological effects of reading an electronic book on a light-emitting device (LE-eBook) with reading a printed book in the hours before bedtime. Participants reading an LE-eBook took longer to fall asleep and had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock, and reduced next-morning alertness than when reading a printed book. These results demonstrate that evening exposure to an LE-eBook phase-delays the circadian clock, acutely suppresses melatonin, and has important implications for understanding the impact of such technologies on sleep, performance, health, and safety.

Sex difference in the near-24-hour intrinsic period of the human circadian timing system

The circadian rhythms of melatonin and body temperature are set to an earlier hour in women than in men, even when the women and men maintain nearly identical and consistent bedtimes and wake times. Moreover, women tend to wake up earlier than men and exhibit a greater preference for morning activities than men. Although the neurobiological mechanism underlying this sex difference in circadian alignment is unknown, multiple studies in nonhuman animals have demonstrated a sex difference in circadian period that could account for such a difference in circadian alignment between women and men. Whether a sex difference in intrinsic circadian period in humans underlies the difference in circadian alignment between men and women is unknown. We analyzed precise estimates of intrinsic circadian period collected from 157 individuals (52 women, 105 men; aged 18–74 y) studied in a month-long inpatient protocol designed to minimize confounding influences on circadian period estimation. Overall, the average intrinsic period of the melatonin and temperature rhythms in this population was very close to 24 h [24.15 ± 0.2 h (24 h 9 min ± 12 min)]. We further found that the intrinsic circadian period was significantly shorter in women [24.09 ± 0.2 h (24 h 5 min ± 12 min)] than in men [24.19 ± 0.2 h (24 h 11 min ± 12 min); P < 0.01] and that a significantly greater proportion of women have intrinsic circadian periods shorter than 24.0 h (35% vs. 14%; P < 0.01). The shorter average intrinsic circadian period observed in women may have implications for understanding sex differences in habitual sleep duration and insomnia prevalence.

Human responses to bright light of different durations

•  Light is the strongest time cue for entrainment and phase resetting of the circadian clock. •  In humans, exposure to long‐duration light (6.5 h) in the late evening/early night causes phase delays, suppresses melatonin and increases alertness. •  Here we studied the effects of different durations of exposure to a single high‐intensity (∼10,000 lux) light pulse (0.2 h, 1 h, 2.5 h and 4.0 h) on phase shifting, suppression of melatonin and self‐reported sleepiness in young men and women. •  Phase‐resetting and melatonin‐suppression responses were dose dependent and non‐linear; shorter light exposures more efficiently phase‐shift the clock, suppress melatonin and induce alertness.

The human circadian system adapts to prior photic history.

Non‐technical summary  The human biological clock organizes and regulates the timing of many biochemical and physiological processes, including the timing of sleep, on a daily basis. Light is the strongest time cue to the circadian clock that keeps these rhythms entrained to the 24 h day. Light exposure at night results in ‘resetting’ of the clock (phase shifting). In the current study, we examined the effects of exposing subjects to two different light levels (very dim light vs. typical room light) before exposure to a 6.5 h light exposure at night. Results showed that the very dim light level, compared to the typical room light level, prior to the light exposure at night caused a substantially greater phase shift of the melatonin rhythm and substantially greater acute melatonin suppression. Thus, prior dim light history sensitizes the human biological clock to the effect of a subsequent light exposure.

Sleep Timing and Circadian Phase in Delayed Sleep Phase Syndrome

Delayed sleep phase syndrome (DSPS) is a circadian rhythm sleep disorder in which the timing of the sleep episode occurs later than desired and is associated with difficulty falling asleep, problems awakening on time (e.g., to meet work or school obligations), and daytime sleepiness. The phase relationship between the timing of sleep and endogenous circadian rhythms is critical to the initiation and maintenance of sleep, and significant alteration leads to impairment of sleep quality and duration. The aim of this retrospective study was to determine the phase relationship between sleep-wake times and physiological markers of circadian timing in clinic patients with DSPS. Objective and subjective measures of sleep timing and circadian phase markers (core body temperature and melatonin) were measured in patients with DSPS and compared with age-matched controls. As expected, significant delays in the timing of the major sleep episode and circadian phase of body temperature and melatonin rhythms were seen in the DSPS group when allowed to sleep at their own habitual schedules, but the phase relationship between sleep-wake times and circadian phase was similar between the 2 groups. These results suggest that the symptoms of insomnia and excessive daytime sleepiness in DSPS patients living under entrained real-life conditions cannot be explained by an alteration in the phase relationship between sleep-wake patterns and other physiological circadian rhythms.

Locomotor response to an open field during C57BL/6J active and inactive phases: differences dependent on conditions of illumination.

Time of day has proven to be a source of variability in diverse behavioral measures. Knowledge of the pattern of this temporal effect as well as its origin (exogenous or endogenous) is essential for a precise description of any behavior. This study analyzed the effect of the external light-dark cycle and the internal rest-activity rhythm on the response of C57BL/6J mice to a novel environment. In a first experiment, animals maintained in a 12:12-h light-dark cycle were tested in an open field at six different times of day. A diurnal rhythm of ambulation in the open field was observed with greater levels of activity exhibited by those groups tested at night. Long-term and short-term behavioral habituation to spatial novelty were also affected by phase of the light-dark cycle. A second experiment was designed to control for any direct effect of the light-dark cycle by keeping the animals in dim green light where entrainment was maintained by a skeleton photoperiod (two 15-min bright-light pulses separated by 12 hours of green, dim light). This second group of animals was tested at two different circadian phases under the same conditions of illumination. One group was tested during the subjective night and another group during the subjective day, i.e., 2 or 14 h after the onset of the active phase, as assessed by wheel-running behavior. No effect of circadian phase on ambulation or habituation of this response to the open field was observed in these animals. Taken together, these results suggest that spatial novelty is equally arousing regardless of circadian phase and that the conditions of illumination can dramatically alter the response to a novel environment.

Direct effects of light on alertness, vigilance, and the waking electroencephalogram in humans depend on prior light history.

STUDY OBJECTIVES Light can induce an acute alerting response in humans; however, it is unknown whether the magnitude of this response is simply a function of the absolute illuminance of the light itself, or whether it depends on illuminance history preceding the stimulus. Here, we compared the effects of illuminance history on the alerting response to a subsequent light stimulus. DESIGN A randomized, crossover design was used to compare the effect of two illuminance histories (1 lux vs. 90 lux) on the alerting response to a 6.5-h 90-lux light stimulus during the biological night. SETTING Intensive Physiologic Monitoring Unit, Brigham and Womens Hospital, Boston, MA. PARTICIPANTS Fourteen healthy young adults (6 F; 23.5 ± 2.9 years). INTERVENTIONS Participants were administered two 6.5-h light exposures (LE) of 90 lux during the biological night. For 3 days prior to each LE, participants were exposed to either 1 lux or 90 lux during the wake episode. MEASUREMENTS AND RESULTS The alerting response to light was assessed using subjective sleepiness ratings, lapses of attention, and reaction times as measured with an auditory psychomotor vigilance task, as well as power density in the delta/theta range of the waking EEG. The alerting response to light was greater and lasted longer when the LE followed exposure to 1 lux compared to 90 lux light. CONCLUSION The magnitude and duration of the alerting effect of light at night depends on the illuminance history and appears to be subject to sensitization and adaptation.

A common polymorphism near PER1 and the timing of human behavioral rhythms

Circadian rhythms influence the timing of behavior, neurological diseases, and even death. Rare mutations in homologs of evolutionarily conserved clock genes are found in select pedigrees with extreme sleep timing, and there is suggestive evidence that certain common polymorphisms may be associated with self‐reported day/night preference. However, no common polymorphism has been associated with the timing of directly observed human behavioral rhythms or other physiological markers of circadian timing at the population level.

Circadian rhythm sleep disorders.

Circadian rhythm sleep disorders are characterized by abnormal timing of the major sleep period that results in complaints of insomnia and excessive daytime sleepiness. Evidence suggests that these disorders result from alterations in the circadian timing system and potentially in the sleep homeostatic process. Some of these disorders are familial in nature and may be the result of alterations in the function of circadian clock genes. Treatments are limited for these disorders because of a lack of practical diagnostic tools to assess circadian function, and randomized controlled clinical trials. Further studies of the pathophysiology of circadian rhythm sleep disorders are necessary for the development of improved treatments.

Impact of common diabetes risk variant in MTNR1B on sleep, circadian and melatonin physiology

The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive in-laboratory protocols (n = 58–96) or cross-sectional studies with sleep quantity and quality and timing measures from self-report (n = 4,307–10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021). In the in-laboratory studies, we found a significant association with a substantially longer duration of elevated melatonin levels (41 min) and delayed circadian phase of dim-light melatonin offset (1.37 h), partially mediated through delayed offset of melatonin synthesis. Furthermore, increased T2D risk in MTNR1B risk allele carriers was more pronounced in early risers versus late risers as determined by 7 days of actigraphy. Our results provide the surprising insight that the MTNR1B risk allele influences dynamics of melatonin secretion, generating a novel hypothesis that the MTNR1B risk allele may extend the duration of endogenous melatonin production later into the morning and that early waking may magnify the diabetes risk conferred by the risk allele.