Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults.

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert scientific consensus and expressed in an easily measured quantity (melanopic equivalent daylight illuminance (melaponic EDI)) defined within this standard. The recommendations are supported by detailed analysis of the sensitivity of human circadian, neuroendocrine, and alerting responses to ocular light and provide a straightforward framework to inform lighting design and practice.

The spectral sensitivity of human circadian phase resetting and melatonin suppression to light changes dynamically with light duration.

Human circadian, neuroendocrine, and neurobehavioral responses to light are mediated primarily by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs) but they also receive input from visual photoreceptors. Relative photoreceptor contributions are irradiance- and duration-dependent but results for long-duration light exposures are limited. We constructed irradiance-response curves and action spectra for melatonin suppression and circadian resetting responses in participants exposed to 6.5-h monochromatic 420, 460, 480, 507, 555, or 620 nm light exposures initiated near the onset of nocturnal melatonin secretion. Melatonin suppression and phase resetting action spectra were best fit by a single-opsin template with lambdamax at 481 and 483 nm, respectively. Linear combinations of melanopsin (ipRGC), short-wavelength (S) cone, and combined long- and medium-wavelength (L+M) cone functions were also fit and compared. For melatonin suppression, lambdamax was 441 nm in the first quarter of the 6.5-h exposure with a second peak at 550 nm, suggesting strong initial S and L+M cone contribution. This contribution decayed over time; lambdamax was 485 nm in the final quarter of light exposure, consistent with a predominant melanopsin contribution. Similarly, for circadian resetting, lambdamax ranged from 445 nm (all three functions) to 487 nm (L+M-cone and melanopsin functions only), suggesting significant S-cone contribution, consistent with recent model findings that the first few minutes of a light exposure drive the majority of the phase resetting response. These findings suggest a possible initial strong cone contribution in driving melatonin suppression and phase resetting, followed by a dominant melanopsin contribution over longer duration light exposures.

Circadian rhythms and disorders of the timing of sleep.

The daily alternation between sleep and wakefulness is one of the most dominant features of our lives and is a manifestation of the intrinsic 24 h rhythmicity underlying almost every aspect of our physiology. Circadian rhythms are generated by networks of molecular oscillators in the brain and peripheral tissues that interact with environmental and behavioural cycles to promote the occurrence of sleep during the environmental night. This alignment is often disturbed, however, by contemporary changes to our living environments, work or social schedules, patterns of light exposure, and biological factors, with consequences not only for sleep timing but also for our physical and mental health. Characterised by undesirable or irregular timing of sleep and wakefulness, in this Series paper we critically examine the existing categories of circadian rhythm sleep-wake disorders and the role of the circadian system in their development. We emphasise how not all disruption to daily rhythms is driven solely by an underlying circadian disturbance, and take a broader, dimensional approach to explore how circadian rhythms and sleep homoeostasis interact with behavioural and environmental factors. Very few high-quality epidemiological and intervention studies exist, and wider recognition and treatment of sleep timing disorders are currently hindered by a scarcity of accessible and objective tools for quantifying sleep and circadian physiology and environmental variables. We therefore assess emerging wearable technology, transcriptomics, and mathematical modelling approaches that promise to accelerate the integration of our knowledge in sleep and circadian science into improved human health.

Effect on Patient Safety of a Resident Physician Schedule without 24-Hour Shifts.

BACKGROUND: The effects on patient safety of eliminating extended-duration work shifts for resident physicians remain controversial. METHODS: We conducted a multicenter, cluster-randomized, crossover trial comparing two schedules for pediatric resident physicians during their intensive care unit (ICU) rotations: extended-duration work schedules that included shifts of 24 hours or more (control schedules) and schedules that eliminated extended shifts and cycled resident physicians through day and night shifts of 16 hours or less (intervention schedules). The primary outcome was serious medical errors made by resident physicians, assessed by intensive surveillance, including direct observation and chart review. RESULTS: The characteristics of ICU patients during the two work schedules were similar, but resident physician workload, described as the mean (±SD) number of ICU patients per resident physician, was higher during the intervention schedules than during the control schedules (8.8±2.8 vs. 6.7±2.2). Resident physicians made more serious errors during the intervention schedules than during the control schedules (97.1 vs. 79.0 per 1000 patient-days; relative risk, 1.53; 95% confidence interval [CI], 1.37 to 1.72; P<0.001). The number of serious errors unitwide were likewise higher during the intervention schedules (181.3 vs. 131.5 per 1000 patient-days; relative risk, 1.56; 95% CI, 1.43 to 1.71). There was wide variability among sites, however; errors were lower during intervention schedules than during control schedules at one site, rates were similar during the two schedules at two sites, and rates were higher during intervention schedules than during control schedules at three sites. In a secondary analysis that was adjusted for the number of patients per resident physician as a potential confounder, intervention schedules were no longer associated with an increase in errors. CONCLUSIONS: Contrary to our hypothesis, resident physicians who were randomly assigned to schedules that eliminated extended shifts made more serious errors than resident physicians assigned to schedules with extended shifts, although the effect varied by site. The number of ICU patients cared for by each resident physician was higher during schedules that eliminated extended shifts. (Funded by the National Heart, Lung, and Blood Institute; ROSTERS ClinicalTrials.gov number, NCT02134847.).

Invited Commentary: There's No Place Like Home-Integrating a Place-Based Approach to Understanding Sleep.

Light exposure at night impedes sleep and shifts the circadian clock. An extensive body of literature has linked sleep deprivation and circadian misalignment with cardiac disease, cancer, mental health disorders, and other chronic illnesses, as well as more immediate risks, such as motor vehicle crashes and occupational injuries. In this issue of the Journal, Zhong et al. (Am J Epidemiol. 2022;191(9):1532-1539) build on this literature, finding that in a cohort of 50,000 California teachers, artificial light at night, noise, green space, and air pollution were all associated with sleep disturbances. Light, noise, air pollution, and the lack of green space are problems inequitably distributed across the population, concentrated among vulnerable populations in inner cities. Zhong et al. provide novel data on the manner in which these local environmental exposures drive sleep deprivation. Future research should explore the degree to which place-based disparities in sleep in turn drive disparities in short and long-term health. Addressing home-based sleep disparities could be an avenue to addressing systemic racism and achieving environmental justice.

Dynamic lighting schedules to facilitate circadian adaptation to shifted timing of sleep and wake.

Circadian adaptation to shifted sleep/wake schedules may be facilitated by optimizing the timing, intensity and spectral characteristics of light exposure, which is the principal time cue for mammalian circadian pacemaker, and possibly by strategically timing nonphotic time cues such as exercise. Therefore, circadian phase resetting by light and exercise was assessed in 44 healthy participants (22 females, mean age [±SD] 36.2 ± 9.2 years), who completed 8-day inpatient experiments simulating night shiftwork, which included either an 8 h advance or 8 h delay in sleep/wake schedules. In the advance protocol (n = 18), schedules were shifted either gradually (1.6 h/day across 5 days) or abruptly (slam shift, 8 h in 1 day and maintained across 5 days). Both advance protocols included a dynamic lighting schedule (DLS) with 6.5 h exposure of blue-enriched white light (704 melanopic equivalent daylight illuminance [melEDI] lux) during the day and dimmer blue-depleted light (26 melEDI lux) for 2 h immediately before sleep on the shifted schedule. In the delay protocol (n = 26), schedules were only abruptly delayed but included four different lighting conditions: (1) 8 h continuous room-light control; (2) 8 h continuous blue-enriched light; (3) intermittent (7 × 15 min pulses/8 h) blue-enriched light; (4) 8 h continuous blue-enriched light plus moderate intensity exercise. In the room-light control, participants received dimmer white light for 30 min before bedtime, whereas in the other three delay protocols participants received dimmer blue-depleted light for 30 min before bedtime. Both the slam and gradual advance protocols induced similar shifts in circadian phase (3.28 h ± 0.37 vs. 2.88 h ± 0.31, respectively, p = .43) estimated by the change in the timing of timing of dim light melatonin onset. In the delay protocol, the continuous 8 h blue-enriched exposure induced significantly larger shifts than the room light control (-6.59 h ± 0.43 vs. -4.74 h ± 0.62, respectively, p = .02). The intermittent exposure induced ~60% of the shift (-3.90 h ± 0.62) compared with 8 h blue-enriched continuous light with only 25% of the exposure duration. The addition of exercise to the 8 h continuous blue-enriched light did not result in significantly larger phase shifts (-6.59 h ± 0.43 vs. -6.41 h ± 0.69, p = .80). Collectively, our results demonstrate that, when attempting to adapt to an 8 h overnight work shift, delay shifts are more successful, particularly when accompanied by a DLS with high-melanopic irradiance light stimulus during wake.

Effects of dynamic lighting on circadian phase, self-reported sleep and performance during a 45-day space analog mission with chronic variable sleep deficiency.

Spaceflight exposes crewmembers to circadian misalignment and sleep loss, which impair cognition and increase the risk of errors and accidents. We compared the effects of an experimental dynamic lighting schedule (DLS) with a standard static lighting schedule (SLS) on circadian phase, self-reported sleep and cognition during a 45-day simulated space mission. Sixteen participants (mean age [±SD] 37.4 ± 6.7 years; 5 F; n = 8/lighting condition) were studied in four-person teams at the NASA Human Exploration Research Analog. Participants were scheduled to sleep 8 h/night on two weekend nights, 5 h/night on five weekday nights, repeated for six 7-day cycles, with scheduled waketime fixed at 7:00 a.m. Compared to the SLS where illuminance and spectrum remained constant during wake (~4000K), DLS increased the illuminance and short-wavelength (blue) content of white light (~6000K) approximately threefold in the main workspace (Level 1), until 3 h before bedtime when illuminance was reduced by ~96% and the blue content also reduced throughout (~4000K × 2 h, ~3000K × 1 h) until bedtime. The average (±SE) urinary 6-sulphatoxymelatonin (aMT6s) acrophase time was significantly later in the SLS (6.22 ± 0.34 h) compared to the DLS (4.76 ± 0.53 h) and more variable in SLS compared to DLS (37.2 ± 3.6 min vs. 28.2 ± 2.4 min, respectively, p = .04). Compared to DLS, self-reported sleep was more frequently misaligned relative to circadian phase in SLS RR: 6.75, 95% CI 1.55-29.36, p = .01), but neither self-reported sleep duration nor latency to sleep was different between lighting conditions. Accuracy in the abstract matching and matrix reasoning tests were significantly better in DLS compared to SLS (false discovery rate-adjusted p ≤ .04). Overall, DLS alleviated the drift in circadian phase typically observed in space analog studies and reduced the prevalence of self-reported sleep episodes occurring at an adverse circadian phase. Our results support incorporating DLS in future missions, which may facilitate appropriate circadian alignment and reduce the risk of sleep disruption.

The role of circadian phase in sleep and performance during Antarctic winter expeditions.

The Antarctic environment presents an extreme variation in the natural light-dark cycle which can cause variability in the alignment of the circadian pacemaker with the timing of sleep, causing sleep disruption, and impaired mood and performance. This study assessed the incidence of circadian misalignment and the consequences for sleep, cognition, and psychological health in 51 over-wintering Antarctic expeditioners (45.6 ± 11.9 years) who completed daily sleep diaries, and monthly performance tests and psychological health questionnaires for 6 months. Circadian phase was assessed via monthly 48-h urine collections to assess the 6-sulphatoxymelatonin (aMT6s) rhythm. Although the average individual sleep duration was 7.2 ± 0.8 h, there was substantial sleep deficiency with 41.4% of sleep episodes <7 h and 19.1% <6 h. Circadian phase was highly variable and 34/50 expeditioners had sleep episodes that occurred at an abnormal circadian phase (acrophase outside of the sleep episode), accounting for 18.8% (295/1565) of sleep episodes. Expeditioners slept significantly less when misaligned (6.1 ± 1.3 h), compared with when aligned (7.3 ± 1.0 h; p < .0001). Performance and mood were worse when awake closer to the aMT6s peak and with increased time awake (all p < .0005). This research highlights the high incidence of circadian misalignment in Antarctic over-wintering expeditioners. Similar incidence has been observed in long-duration space flight, reinforcing the fidelity of Antarctica as a space analog. Circadian misalignment has considerable safety implications, and potentially longer term health risks for other circadian-controlled physiological systems. This increased risk highlights the need for preventative interventions, such as proactively planned lighting solutions, to ensure circadian alignment during long-duration Antarctic and space missions.

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 (>300 lux) or dim (<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 (<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.

Exploratory assessment of pineal gland volume, composition, and urinary 6-sulfatoxymelatonin levels on prostate cancer risk.

INTRODUCTION: Melatonin levels are partially driven by the parenchyma volume of the pineal gland. Low urinary levels of 6-sulfatoxymelatonin have been associated with increased risk of advanced prostate cancer, but the relationship between pineal gland volume and composition and prostate cancer risk has not been examined. MATERIALS AND METHODS: We utilized data from 864 men from the AGES-Reykjavik Study with complete pineal gland volumes and urinary 6-sulfatoxymelatonin measurements. Pineal parenchyma, calcification, and cyst volumes were calculated from brain magnetic resonance imaging. Levels of 6-sulfatoxymelatonin were assayed from prediagnostic urine samples. We calculated Pearson correlation coefficients between parenchyma volume and urinary 6-sulfatoxymelatonin levels. We used Cox proportional hazards regression to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) comparing prostate cancer risk across parenchyma volume tertiles and across categories factoring in parenchyma volume, gland composition, and urinary 6-sulfatoxymelatonin level. RESULTS: Parenchyma volume was moderately correlated with urinary 6-sulfatoxymelatonin level (r = .24; p < .01). There was no statistically significant association between parenchyma volume tertile and prostate cancer risk. Men with high parenchyma volume, pineal cysts and calcifications, and low urinary 6-sulfatoxymelatonin levels had almost twice the risk of total prostate cancer as men with low parenchyma volume, no pineal calcifications or cysts, and low urinary 6-sulfatoxymelatonin levels (HR: 1.98; 95% CI: 1.02, 3.84; p: .04). CONCLUSIONS: Although parenchyma volume is not associated with prostate cancer risk, pineal gland composition and other circadian dynamics may influence risk for prostate cancer. Additional studies are needed to examine the interplay of pineal gland volume, composition, and melatonin levels on prostate cancer risk.

The impact of the wake maintenance zone on attentional capacity, physiological drowsiness, and subjective task demands during sleep deprivation.

We aimed to investigate the impact of the Wake Maintenance Zone (WMZ) on measures of drowsiness, attention, and subjective performance under rested and sleep deprived conditions. We studied 23 healthy young adults (18 males; mean age = 25.41 ± 5.73 years) during 40 hr of total sleep deprivation under constant routine conditions. Participants completed assessments of physiological drowsiness (EEG-scored slow eye movements and microsleeps), sustained attention (PVT), and subjective task demands every two hours, and four-hourly ocular motor assessment of inhibitory control (inhibition of reflexive saccades on an anti-saccade task). Tests were analyzed relative to dim light melatonin onset (DLMO); the WMZ was defined as the 3 hr prior to DLMO, and the preceding 3 hr window was deemed the pre-WMZ. The WMZ did not mitigate the adverse impact of ~37 hr sleep deprivation on drowsiness, sustained attention, response inhibition, and self-rated concentration and difficulty, relative to rested WMZ performance (~13 hr of wakefulness). Compared to the pre-WMZ, though, the WMZ improved measures of sustained attention, and subjective concentration and task difficulty, during sleep deprivation. Cumulatively, these results expand on previous work by characterizing the beneficial effects of the WMZ on operationally-relevant indices of drowsiness, inhibitory attention control, and self-rated concentration and task difficulty relative to the pre-WMZ during sleep deprivation. These results may inform scheduling safety-critical tasks at more optimal circadian times to improve workplace performance and safety.

Breast cancer and circadian disruption from electric lighting in the modern world.

Breast cancer is the leading cause of cancer death among women worldwide, and there is only a limited explanation of why. Risk is highest in the most industrialized countries but also is rising rapidly in the developing world. Known risk factors account for only a portion of the incidence in the high-risk populations, and there has been considerable speculation and many false leads on other possibly major determinants of risk, such as dietary fat. A hallmark of industrialization is the increasing use of electricity to light the night, both within the home and without. It has only recently become clear that this evolutionarily new and, thereby, unnatural exposure can disrupt human circadian rhythmicity, of which three salient features are melatonin production, sleep, and the circadian clock. A convergence of research in cells, rodents, and humans suggests that the health consequences of circadian disruption may be substantial. An innovative experimental model has shown that light at night markedly increases the growth of human breast cancer xenografts in rats. In humans, the theory that light exposure at night increases breast cancer risk leads to specific predictions that are being tested epidemiologically: evidence has accumulated on risk in shift workers, risk in blind women, and the impact of sleep duration on risk. If electric light at night does explain a portion of the breast cancer burden, then there are practical interventions that can be implemented, including more selective use of light and the adoption of recent advances in lighting technology and application.

Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers.

Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40 hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8 hours sleep at night, four meals during a 16 hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n = 16 males, mean age ± SD = 23.4 ± 2.3 years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n = 25, 14 females, 36.3 ± 8.9 years) across four protocols; two with abrupt 8 hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8 hour advance (1.6 hours/day over 5 days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7 hours and -4.2 hours, respectively, compared to -6.6 hours and -4.7 hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1 hours) but not the gradual (+2.1 hours) protocol, compared to +3.1 hours and +2.8 hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.

In-person vs home schooling during the COVID-19 pandemic: Differences in sleep, circadian timing, and mood in early adolescence.

During the COVID-19 pandemic, schools around the world rapidly transitioned from in-person to remote learning, providing an opportunity to examine the impact of in-person vs remote learning on sleep, circadian timing, and mood. We assessed sleep-wake timing using wrist actigraphy and sleep diaries over 1-2 weeks during in-person learning (n = 28) and remote learning (n = 58, where n = 27 were repeat assessments) in adolescents (age M ± SD = 12.79 ± 0.42 years). Circadian timing was measured under a single condition in each individual using salivary melatonin (Dim Light Melatonin Onset; DLMO). Online surveys assessed mood (PROMIS Pediatric Anxiety and Depressive Symptoms) and sleepiness (Epworth Sleepiness Scale - Child and Adolescent) in each condition. During remote (vs in-person) learning: (i) on school days, students went to sleep 26 minutes later and woke 49 minutes later, resulting in 22 minutes longer sleep duration (all P < .0001); (ii) DLMO time did not differ significantly between conditions, although participants woke at a later circadian phase (43 minutes, P = .03) during remote learning; and (iii) participants reported significantly lower sleepiness (P = .048) and lower anxiety symptoms (P = .006). Depressive symptoms did not differ between conditions. Changes in mood symptoms were not mediated by sleep. Although remote learning continued to have fixed school start times, removing morning commutes likely enabled adolescents to sleep longer, wake later, and to wake at a later circadian phase. These results indicate that remote learning, or later school start times, may extend sleep and improve some subjective symptoms in adolescents.

Home-based light therapy for fatigue following acquired brain injury: a pilot randomized controlled trial.

BACKGROUND AND OBJECTIVES: Fatigue and sleep disturbance are debilitating problems following brain injury and there are no established treatments. Building on demonstrated efficacy of blue light delivered via a lightbox in reducing fatigue and daytime sleepiness after TBI, this study evaluated the efficacy of a novel in-home light intervention in alleviating fatigue, sleep disturbance, daytime sleepiness and depressive symptoms, and in improving psychomotor vigilance and participation in daily productive activity, following injury METHODS: The impact of exposure to a dynamic light intervention (Treatment) was compared to usual lighting (Control) in a randomized within-subject, crossover trial. Outcomes were fatigue (primary outcome), daytime sleepiness, sleep disturbance, insomnia symptoms, psychomotor vigilance, mood and activity levels. Participants (N = 24, M ± SDage = 44.3 ± 11.4) had mild-severe TBI or stroke > 3 months previously, and self-reported fatigue (Fatigue Severity Scale ≥ 4). Following 2-week baseline, participants completed each condition for 2 months in counter-balanced order, with 1-month follow-up. Treatment comprised daytime blue-enriched white light (CCT > 5000 K) and blue-depleted light (< 3000 K) 3 h prior to sleep. RESULTS: Random-effects mixed-model analysis showed no significantly greater change in fatigue on the Brief Fatigue Inventory during Treatment, but a medium effect size of improvement (p = .33, d = -0.42). There were significantly greater decreases in sleep disturbance (p = .004), insomnia symptoms (p = .036), reaction time (p = .004) and improvements in productive activity (p = .005) at end of Treatment relative to Control, with large effect sizes (d > 0.80). Changes in other outcomes were non-significant. CONCLUSIONS: This pilot study provides preliminary support for in-home dynamic light therapy to address sleep-related symptoms in acquired brain injury. TRIAL REGISTRATION: This trial was registered with the Australian and New Zealand Clinical Trials Registry on 13 June 2017, www.anzctr.org.au , ACTRN12617000866303.

Exploring the associations between shift work disorder, depression, anxiety and sick leave taken amongst nurses.

This study aimed to evaluate the association between shift work disorder and mental health in hospital-based nurses. Staff completed an online survey comprising demographic questions, the Shift Work Disorder Questionnaire, Patient Health-9 and the General Anxiety Disorder-7 scale. Sick leave data were collected from archival records from the Human Resources Department. Two hundred and two nurses (95% female; age M = 35.28 years ± SD = 12) participated (42% of eligible staff). Those at high risk of shift work disorder had higher depression (M = 7.54 ± SD = 4.28 vs. M = 3.78 ± SD = 3.24; p < 0.001) and anxiety (M = 5.66 ± SD = 3.82 vs. M = 2.83 ± SD = 3.33, p < 0.001) compared to those at low risk. Linear regression models showed that being at high risk of shift work disorder was the most significant predictor of depression, explaining 18.8% of the variance in depression (R2  = 0.188, adjusted R2  = 0.184, F(1, 200) = 46.20, p < 0.001). Shift work disorder combined with the number of night shifts and alcoholic drinks on non-work days accounted for 49.7% of the variance in anxiety scores (R2  = 0.497, adjusted R2  = 0.453, F(3, 35) = 11.51, p < 0.001). Mean sick leave in those with high risk of shift work disorder was 136.17 hr (SD = 113.11) versus 103.98 hr (SD = 94.46) in others (p = 0.057). Depression and years of shift work accounted for 18.9% of the variance in sick leave taken (R2  = 0.189, adjusted R2  = 0.180, F(2, 175) = 20.36, p < 0.001). Shift work disorder is strongly associated with depression and anxiety, providing a potential target to improve mental health in shift workers. Depression, in turn, is a significant contributing factor to sick leave.

Modeling melanopsin-mediated effects of light on circadian phase, melatonin suppression, and subjective sleepiness.

A physiologically based model of arousal dynamics is improved to incorporate the effects of the light spectrum on circadian phase resetting, melatonin suppression, and subjective sleepiness. To account for these nonvisual effects of light, melanopic irradiance replaces photopic illuminance that was used previously in the model. The dynamic circadian oscillator is revised according to the melanopic irradiance definition and tested against experimental circadian phase resetting dose-response and phase response data. Melatonin suppression function is recalibrated against melatonin dose-response data for monochromatic and polychromatic light sources. A new light-dependent term is introduced into the homeostatic weight component of subjective sleepiness to represent the direct alerting effect of light; the new term responds to light change in a time-dependent manner and is calibrated against experimental data. The model predictions are compared to a total of 14 experimental studies containing 26 data sets for 14 different spectral light profiles. The revised melanopic model shows on average 1.4 times lower prediction error for circadian phase resetting compared to the photopic-based model, 3.2 times lower error for melatonin suppression, and 2.1 times lower error for subjective sleepiness. Overall, incorporating melanopic irradiance allowed simulation of wavelength-dependent responses to light and could explain the majority of the observations. Moving forward, models of circadian phase resetting and the direct effects of light on alertness and sleep need to use nonvisual photoreception-based measures of light, for example, melanopic irradiance, instead of the traditionally used illuminance based on the visual system.

A PERIOD3 variable number tandem repeat polymorphism modulates melatonin treatment response in delayed sleep-wake phase disorder.

We examined whether a polymorphism of the PERIOD3 gene (PER3; rs57875989) modulated the sleep-promoting effects of melatonin in Delayed Sleep-Wake Phase Disorder (DSWPD). One hundred and four individuals (53 males; 29.4 ±10.0 years) with DSWPD and a delayed dim light melatonin onset (DLMO) collected buccal swabs for genotyping (PER34/4 n = 43; PER3 5 allele [heterozygous and homozygous] n = 60). Participants were randomised to placebo or 0.5 mg melatonin taken 1 hour before desired bedtime (or ~1.45 hours before DLMO), with sleep attempted at desired bedtime (4 weeks; 5-7 nights/week). We assessed sleep (diary and actigraphy), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Patient-Reported Outcomes Measurement Information System (PROMIS: Sleep Disturbance, Sleep-Related Impairment), Sheehan Disability Scale (SDS) and Patient- and Clinician-Global Improvement (PGI-C, CGI-C). Melatonin treatment response on actigraphic sleep onset time did not differ between genotypes. For PER34/4 carriers, self-reported sleep onset time was advanced by a larger amount and sleep onset latency (SOL) was shorter in melatonin-treated patients compared to those receiving placebo (P = .008), while actigraphic sleep efficiency in the first third of the sleep episode (SE T1) did not differ. For PER3 5 carriers, actigraphic SOL and SE T1 showed a larger improvement with melatonin (P < .001). Melatonin improved ISI (P = .005), PROMIS sleep disturbance (P < .001) and sleep-related impairment (P = .017), SDS (P = .019), PGI-C (P = .028) and CGI-C (P = .016) in PER34/4 individuals only. Melatonin did not advance circadian phase. Overall, PER34/4 DSWPD patients have a greater response to melatonin treatment. PER3 genotyping may therefore improve DSWPD patient outcomes.

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.

Relationship between melatonin and bone resorption rhythms in premenopausal women.

Although evidence exists for a daily rhythm in bone metabolism, the contribution of factors such as melatonin levels, the light-dark cycle, and the sleep-wake cycle is difficult to differentiate given their highly correlated time courses. To examine these influences on bone resorption, we collected 48-h sequential urine samples under both ambulatory (8-h sleep:16-h wake) and constant routine (CR) (constant wake, posture, nutrition and dim light) conditions from 20 healthy premenopausal women. Urinary 6-sulphatoxymelatonin (aMT6s; ng/h) and the bone resorption marker amino-terminal cross-linked collagen I telopeptide (NTx; bone collagen equivalents nM/h) were assayed and fit by cosinor models to determine significant 24-h rhythms and acrophase. Most participants had significant 24-h aMT6s rhythms during both ambulatory and CR conditions (95 and 85%, respectively), but fewer had significant 24-h NTx rhythms (70 and 70%, respectively). Among individuals with significant rhythms, mean (± SD) aMT6s acrophase times were 3:57 ± 1:50 and 3:43 ± 1:25 h under ambulatory and CR conditions, respectively, and 23:44 ± 5:55 and 3:06 ± 5:15 h, respectively, for NTx. Mean 24-h levels of both aMT6s and NTx were significantly higher during CR compared with ambulatory conditions (p < 0.0001 and p = 0.03, respectively). Menstrual phase (follicular versus luteal) had no impact on aMT6s or NTx timing or 24-h levels. This study confirms an endogenous circadian rhythm in NTx with a night-time peak when measured under CR conditions, but also confirms that environmental factors such as the sleep-wake or light-dark cycles, posture or meal timing affects overall concentrations and peak timing under ambulatory conditions, the significance of which remains unclear.