Sleep, health, and society: From aetiology to public health

Sleep disturbances are common in modern society. Since the beginning of the century, populations have shown a decline in sleep duration, owing to changes in environmental and social conditions. Industry was the first to appreciate the detrimental effects of sleep disturbances on health and wellbeing. It has taken, however, many decades to understand the implications for individuals and populations of sustained sleep deprivation. This second edition follows in the footsteps of the first edition published in 2010. It maintains the focus on sleep disturbances as a universal behaviour that affects health and wellbeing in the short and long term, from childhood to adulthood to older age. It provides updates on new topics, such as sleep and cognition, epilepsy, pregnancy, cancer, pain, drowsy driving, built environment, and school times, with historical perspectives and a personal account. It is written in an accessible prose for a general readership, yet maintaining scientific rigour. © Oxford University Press 2018. All Rights Reserved

Daytime exposure to short- and medium-wavelength light did not improve alertness and neurobehavioral performance

While previous studies have demonstrated short-wavelength sensitivity to the acute alerting effects of light during the biological night, fewer studies have assessed the alerting effect of light during the daytime. This study assessed the wavelength-dependent sensitivity of the acute alerting effects of daytime light exposure following chronic sleep restriction in 60 young adults (29 men, 31 women; 22.5 ± 3.1 mean ± SD years). Participants were restricted to 5 h time in bed the night before laboratory admission and 3 h time in bed in the laboratory, aligned by wake time. Participants were randomized for exposure to 3 h total of either narrowband blue (λmax 458-480 nm, n = 23) or green light (λmax 551-555 nm, n = 25) of equal photon densities (2.8-8.4 � 1013 photons/cm2/sec), beginning 3.25 h after waking, and compared with a darkness control (0 lux, n = 12). Subjective sleepiness (Karolinska Sleepiness Scale), sustained attention (auditory Psychomotor Vigilance Task), mood (Profile of Mood States Bi-Polar form), working memory (2-back task), selective attention (Stroop task), and polysomnographic and ocular sleepiness measures (Optalert) were assessed prior to, during, and after light exposure. We found no significant effect of light wavelength on these measures, with the exception of a single mood subscale. Further research is needed to optimize the characteristics of lighting systems to induce alerting effects during the daytime, taking into account potential interactions between homeostatic sleep pressure, circadian phase, and light responsiveness. © SAGE Publications

Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light

10.1126/scitranslmed.3000741Science Translational Medicine23131ra33

Endogenous Circadian Regulation of Female Reproductive Hormones

Context: Studies suggest that female reproductive hormones are under circadian regulation, although methodological differences have led to inconsistent findings. Objective: To determine whether circulating levels of reproductive hormones exhibit circadian rhythms. Design: Blood samples were collected across �90 consecutive hours, including 2 baseline days under a standard sleep-wake schedule and �50 hours of extended wake under constant routine (CR) conditions. Setting: Intensive Physiological Monitoring Unit, Brigham and Women's Hospital. Participants: Seventeen healthy premenopausal women (22.8 ± 2.6 years; nine follicular; eight luteal). Interventions: Fifty-hour CR. Main Outcome Measures: Plasma estradiol (E2), progesterone (P4), LH, FSH, SHBG, melatonin, and core body temperature. Results: All hormones exhibited significant 24-hour rhythms under both standard sleep-wake and CR conditions during the follicular phase (P < 0.05). In contrast, only FSH and SHBG were significantly rhythmic during the luteal phase. Rhythm acrophases and amplitudes were similar between standard sleep-wake and CR conditions. The acrophase occurred in the morning for P4; in the afternoon for FSH, LH, and SHBG; and during the night for E2. Conclusions: Our results confirm previous reports of �24-hour rhythms in many female reproductive hormones in humans under ambulatory conditions but demonstrate that these hormones are under endogenous circadian regulation, defined as persisting in the absence of external time cues. These results may have important implications for the effects of circadian disruption on reproductive function. Copyright © 2019 Endocrine Society

Self-reported drowsiness and safety outcomes while driving after an extended duration work shift in trainee physicians

Study Objectives: Extended duration (�24 hours) work shifts (EDWSs) are associated with increased risk of motor vehicle crashes, and awareness of any impairment has important implications on legal accountability for any adverse driving outcome. The extent to which adverse driving events were preceded by predrive self-reported sleepiness was evaluated in medical residents after an EDWS. Methods: Sixteen resident physicians (10 females; 29.2 ± 2.0 years) working EDWS were monitored when driving on their commute to and from the hospital (438 drives). Sleep and work hours were obtained from daily logs, and adverse driving outcomes were captured from a driving log completed at the end of each drive. Self-reported sleepiness (Karolinska Sleepiness Scale; KSS) and objective drowsiness were captured using a time-stamped, hand-held device and infra-red reflectance oculography. Results: Self-reported sleepiness and objective indices of drowsiness were positively correlated, and both were elevated following EDWSs. Compared with the commute to work, EDWSs were associated with more than double the self-reported adverse outcomes when driving home, significantly higher than drives to or from the day shift at comparable times of day. EDWSs more than tripled the odds of reporting sleep-related, inattentive, hazardous, or violation-driving events. The number and type of adverse event was predicted by the predrive KSS level and in a dose-dependent manner. Conclusions: Driving after an EDWS puts resident physicians/drivers and other road users at avoidable and unnecessary risk. Demonstrating self-reported sleepiness at the beginning of the drive is associated with adverse outcomes has serious implications on the legal accountability for driving when drowsy. © Sleep Research Society 2017

The wake maintenance zone shows task dependent changes in cognitive function following one night without sleep

Study Objectives The interaction between homeostatic sleep pressure and circadian timing modulates the impact of sleep deprivation on cognition. We aimed to investigate how this interaction affects different cognitive functions. Methods Twenty-three healthy volunteers (18 males; mean age = 25.4 ± 5.7 years) underwent 40 hours of sleep deprivation under constant routine conditions. Performance on the Psychomotor Vigilance Test and a cognitive battery assessing vigilant attention, complex attention, recognition memory, and working memory was assessed in the morning (27 hours awake) and evening (37 hours awake) during sleep deprivation and compared to well-rested performance 24 hours earlier. Circadian phase assessments confirmed evening tests occurred in the wake maintenance zone (WMZ). Results Increased time awake significantly impacted performance on all measures except recognition memory. Post hoc analyses found performance on all measures was significantly impaired in the morning following 27 hours of sleep deprivation compared to well-rested performance 24 hours earlier. In contrast, complex attention and working memory were preserved in the WMZ after 37 hours awake compared to 24 hours earlier, while vigilant attention and PVT performance were significantly impaired. During sleep deprivation, composite scores of speed and accuracy were both impaired in the morning, while only speed was impaired during the WMZ. Conclusions We observed task- and time-dependent effects of sleep deprivation, such that vigilant attention was significantly impaired after both 27 hours and 37 hours awake (compared to when well-rested at the same circadian clock time). In contrast, complex attention and working memory were impaired at 27 hours awake, but preserved in the WMZ despite increased homeostatic sleep pressure (37 hours awake). © Sleep Research Society 2018. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please email [email protected]

Associations between sleep disturbances, mental health outcomes and burnout in firefighters, and the mediating role of sleep during overnight work: A cross-sectional study

This study investigated whether sleep disorder risk and mental health outcomes in firefighters were associated with burnout, particularly emotional exhaustion, and examined the mediating role of sleep at work in these relationships. A secondary aim was to investigate associations between habitual sleep characteristics and burnout. North American firefighters (n = 6,307) completed the Maslach Burnout Inventory (emotional exhaustion, depersonalisation, personal accomplishment), and were screened for sleep disorders and self-reported current mental health conditions and sleep characteristics. Multiple logistic regression analyses examined associations between sleep, mental health outcomes and burnout. Firefighters screening positive for a sleep disorder, particularly insomnia, had increased risk of emotional exhaustion (adjusted odds ratio 3.78, 95% confidence interval 2.97�4.79). Firefighters self-reporting a current mental health condition were at greater risk of emotional exhaustion (adjusted odds ratio 3.45, 95% confidence interval 2.79�4.27). Sleep during overnight work mediated the impact of having a sleep disorder and mental health condition on high burnout. Sleepiness and sleep deficit (difference between required and actual sleep), even in firefighters without sleep disorder risk, were associated with depersonalisation (adjusted odds ratio 1.65, 95% confidence interval 1.34�2.03 and adjusted odds ratio 1.29, 95% confidence interval 1.06�1.57, respectively) and low personal accomplishment (adjusted odds ratio 1.25, 95% confidence interval 1.07�1.47 and adjusted odds ratio 1.17, 95% confidence interval 1.01�1.35, respectively). Sleep and mental health problems were associated with increased risk of burnout in firefighters, and sleep during overnight work mediated these relationships. The results suggest the need to examine the effectiveness of occupational interventions that improve the opportunity for sleep, together with screening for and treating sleep disorders, to reduce burnout risk. © 2019 European Sleep Research Societ

High sensitivity and interindividual variability in the response of the human circadian system to evening light

Before the invention of electric lighting, humans were primarily exposed to intense (&gt;300 lux) or dim (&lt;30 lux) environmental light�stimuli at extreme ends of the circadian system�s dose�response curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30�300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose�response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18�30) were exposed to a dim control (&lt;1 lux) and a range of experimental light levels (10�2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock�s role in human health and disease. © 2019 National Academy of Sciences. All rights reserved

Temporal dynamics of circadian phase shifting response to consecutive night shifts in healthcare workers: role of light�dark exposure

Key points: Shift work is highly prevalent and is associated with significant adverse health impacts. There is substantial inter-individual variability in the way the circadian clock responds to changing shift cycles. The mechanisms underlying this variability are not well understood. We tested the hypothesis that light�dark exposure is a significant contributor to this variability; when combined with diurnal preference, the relative timing of light exposure accounted for 71% of individual variability in circadian phase response to night shift work. These results will drive development of personalised approaches to manage circadian disruption among shift workers and other vulnerable populations to potentially reduce the increased risk of disease in these populations. Abstract: Night shift workers show highly variable rates of circadian adaptation. This study examined the relationship between light exposure patterns and the magnitude of circadian phase resetting in response to night shift work. In 21 participants (nursing and medical staff in an intensive care unit) circadian phase was measured using 6-sulphatoxymelatonin at baseline (day/evening shifts or days off) and after 3�4 consecutive night shifts. Daily light exposure was examined relative to individual circadian phase to quantify light intensity in the phase delay and phase advance portions of the light phase response curve (PRC). There was substantial inter-individual variability in the direction and magnitude of phase shift after three or four consecutive night shifts (mean phase delay �1:08 ± 1:31 h; range �3:43 h delay to +3:07 h phase advance). The relative difference in the distribution of light relative to the PRC combined with diurnal preference accounted for 71% of the variability in phase shift. Regression analysis incorporating these factors estimated phase shift to within ±60 min in 85% of participants. No participants met criteria for partial adaptation to night work after three or four consecutive night shifts. Our findings provide evidence that the phase resetting that does occur is based on individual light exposure patterns relative to an individual's baseline circadian phase. Thus, a �one size fits all� approach to promoting adaptation to shift work using light therapy, implemented without knowledge of circadian phase, may not be efficacious for all individuals. © 2018 Monash University. The Journal of Physiology © 2018 The Physiological Societ

Increased sensitivity of the circadian system to light in delayed sleep–wake phase disorder

Patients with delayed sleep�wake phase disorder (DSWPD) exhibit delayed sleep�wake behaviour relative to desired bedtime, often leading to chronic sleep restriction and daytime dysfunction. The majority of DSWPD patients also display delayed circadian timing in the melatonin rhythm. Hypersensitivity of the circadian system to phase-delaying light is a plausible physiological basis for DSWPD vulnerability. We compared the phase shifting response to a 6.5 h light exposure (~150 lux) between male patients with diagnosed DSWPD (n = 10; aged 20.8 ± 2.3 years) and male healthy controls (n = 11; aged 22.4 ± 3.3 years). Salivary dim light melatonin onset (DLMO) was measured under controlled conditions in dim light (<3 lux) before and after light exposure. Correcting for the circadian time of the light exposure, DSWPD patients exhibited 31.5% greater phase delay shifts than healthy controls. In both groups, a later initial melatonin phase was associated with a greater magnitude phase shift, indicating that increased circadian sensitivity to light may be a factor that contributes to delayed phase, even in non-clinical groups. DSWPD patients also had reduced pupil size following the light exposure, and showed a trend towards increased melatonin suppression during light exposure. These findings indicate that, for patients with DSWPD, assessment of light sensitivity may be an important factor that can inform behavioural therapy, including minimization of exposure to phase-delaying night-time light. © 2018 The Authors. The Journal of Physiology and 2018 The Physiological Society