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Concept: Melatonin


The sleep-wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep-wake-dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow-wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift-work, jetlag, and aging.

Concepts: Psychology, Male, Gender, Sleep, Cognition, Circadian rhythm, Jet lag, Melatonin


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.

Concepts: Sleep, Sleep disorder, Circadian rhythm, Electronics, Delayed sleep phase syndrome, Chronotype, Jet lag, Melatonin


Circadian rhythms, metabolism, and nutrition are intimately linked [1, 2], although effects of meal timing on the human circadian system are poorly understood. We investigated the effect of a 5-hr delay in meals on markers of the human master clock and multiple peripheral circadian rhythms. Ten healthy young men undertook a 13-day laboratory protocol. Three meals (breakfast, lunch, dinner) were given at 5-hr intervals, beginning either 0.5 (early) or 5.5 (late) hr after wake. Participants were acclimated to early meals and then switched to late meals for 6 days. After each meal schedule, participants' circadian rhythms were measured in a 37-hr constant routine that removes sleep and environmental rhythms while replacing meals with hourly isocaloric snacks. Meal timing did not alter actigraphic sleep parameters before circadian rhythm measurement. In constant routines, meal timing did not affect rhythms of subjective hunger and sleepiness, master clock markers (plasma melatonin and cortisol), plasma triglycerides, or clock gene expression in whole blood. Following late meals, however, plasma glucose rhythms were delayed by 5.69 ± 1.29 hr (p < 0.001), and average glucose concentration decreased by 0.27 ± 0.05 mM (p < 0.001). In adipose tissue, PER2 mRNA rhythms were delayed by 0.97 ± 0.29 hr (p < 0.01), indicating that human molecular clocks may be regulated by feeding time and could underpin plasma glucose changes. Timed meals therefore play a role in synchronizing peripheral circadian rhythms in humans and may have particular relevance for patients with circadian rhythm disorders, shift workers, and transmeridian travelers.

Concepts: Sleep, Circadian rhythm, Period, ARNTL, Circadian rhythm sleep disorder, Melatonin, Dinner


In spaceflight human circadian rhythms and sleep patterns are likely subject to change, which consequently disturbs human physiology, cognitive abilities and performance efficiency. However, the influence of microgravity on sleep and circadian clock as well as the underlying mechanisms remain largely unknown. Placing volunteers in a prone position, whereby their heads rest at an angle of -6° below horizontal, mimics the microgravity environment in orbital flight. Such positioning is termed head-down bed rest (HDBR). In this work, we analysed the influence of a 45-day HDBR on physiological diurnal rhythms. We examined urinary electrolyte and hormone excretion, and the results show a dramatic elevation of cortisol levels during HDBR and recovery. Increased diuresis, melatonin and testosterone were observed at certain periods during HDBR. In addition, we investigated the changes in urination and defecation frequencies and found that the rhythmicity of urinary frequency during lights-off during and after HDBR was higher than control. The grouped defecation frequency data exhibits rhythmicity before and during HDBR but not after HDBR. Together, these data demonstrate that HDBR can alter a number of physiological processes associated with diurnal rhythms.

Concepts: Physiology, Sleep, Circadian rhythm, Circadian rhythms, Delayed sleep phase syndrome, Chronotype, Diurnality, Melatonin


Although the health burden of shift work has not been extensively studied, evidence suggests that it may affect the metabolic balance and cause obesity and other metabolic disorders. Sleep deprivation, circadian desynchronization and behavioral changes in diet and physical activity are among the most commonly mentioned factors in studies of the association between night work and metabolic disorders. Individual adaptation to night work depends greatly on personal factors such as family and social life, but occupational interventions may also make a positive contribution to the transition to shift work, such as exposure to bright lights during the night shift, melatonin use, shift regularity and clockwise rotation, and dietary adaptations for the metabolic needs of night workers. The evaluation of the impact of night work on health and of the mechanisms underlying this relationship can serve as a basis for intervention strategies to minimize the health burden of shift work. This review aimed to identify highlights regarding therapeutic implications following the association between night and shift work and metabolic disorders, as well as the mechanisms and pathways responsible for these relationships.

Concepts: Nutrition, Obesity, Sleep, Sleep deprivation, Circadian rhythm, Circadian rhythms, Circadian rhythm sleep disorder, Melatonin


The association of irregular sleep schedules with circadian timing and academic performance has not been systematically examined. We studied 61 undergraduates for 30 days using sleep diaries, and quantified sleep regularity using a novel metric, the sleep regularity index (SRI). In the most and least regular quintiles, circadian phase and light exposure were assessed using salivary dim-light melatonin onset (DLMO) and wrist-worn photometry, respectively. DLMO occurred later (00:08 ± 1:54 vs. 21:32 ± 1:48; p < 0.003); the daily sleep propensity rhythm peaked later (06:33 ± 0:19 vs. 04:45 ± 0:11; p < 0.005); and light rhythms had lower amplitude (102 ± 19 lux vs. 179 ± 29 lux; p < 0.005) in Irregular compared to Regular sleepers. A mathematical model of the circadian pacemaker and its response to light was used to demonstrate that Irregular vs. Regular group differences in circadian timing were likely primarily due to their different patterns of light exposure. A positive correlation (r = 0.37; p < 0.004) between academic performance and SRI was observed. These findings show that irregular sleep and light exposure patterns in college students are associated with delayed circadian rhythms and lower academic performance. Moreover, the modeling results reveal that light-based interventions may be therapeutically effective in improving sleep regularity in this population.

Concepts: Sleep, Circadian rhythm, Chronobiology, Circadian rhythms, Delayed sleep phase syndrome, Chronotype, Melatonin, Phase response curve


Although the light-induced melatonin suppression response is well characterized in adults, studies examining the dynamics of this effect in children are scarce. The purpose of this study was to quantify the magnitude of evening light-induced melatonin suppression in preschool-age children. Healthy children (n = 10; 7 females; 4.3 ± 1.1 years) participated in a 7-day protocol. On days 1-5, children followed a strict sleep schedule. On day 6, children entered a dim light environment (<15 lux) for 1-h before providing salivary samples every 20- to 30-min from the afternoon until 50-min after scheduled bedtime. On day 7, subjects remained in dim light conditions until 1-h before bedtime, at which time they were exposed to a bright light stimulus (~1000 lux) for 1-h and then re-entered dim light conditions. Saliva samples were obtained before, during, and after bright light exposure and were time anchored to samples taken the previous evening. We found robust melatonin suppression (87.6 ± 10.0%) in response to the bright light stimulus. Melatonin levels remained attenuated for 50-min after termination of the light stimulus (P < 0.008). Furthermore, melatonin levels did not return to 50% of those observed in the dim light condition 50-min after the light exposure for 7/10 children. Our findings demonstrate a robust light-induced melatonin suppression response in preschool-age children. These findings have implications for understanding the role of evening light exposure in the development of evening settling difficulties and may serve as experimental evidence to support recommendations regarding light exposure and sleep hygiene practices in early childhood.

Concepts: Sleep, Childhood, Circadian rhythm, Hygiene, Delayed sleep phase syndrome, Light therapy, Melatonin, Phase response curve


This study proposes representative figures of merit for circadian and vision performance for healthy and efficient use of smartphone displays. The recently developed figures of merit for circadian luminous efficacy of radiation (CER) and circadian illuminance (CIL) related to human health and circadian rhythm were measured to compare three kinds of commercial smartphone displays. The CIL values for social network service (SNS) messenger screens from all three displays were higher than 41.3 biolux (blx) in a dark room at night, and the highest CIL value reached 50.9 blx. These CIL values corresponded to melatonin suppression values (MSVs) of 7.3% and 11.4%, respectively. Moreover, smartphone use in a bright room at night had much higher CIL and MSV values (58.7 ~ 105.2 blx and 15.4 ~ 36.1%, respectively). This study also analyzed the nonvisual and visual optical properties of the three smartphone displays while varying the distance between the screen and eye and controlling the brightness setting. Finally, a method to possibly attenuate the unhealthy effects of smartphone displays was proposed and investigated by decreasing the emitting wavelength of blue LEDs in a smartphone LCD backlight and subsequently reducing the circadian effect of the display.

Concepts: Medicine, Health, Eye, Light-emitting diode, Lighting, Circadian rhythm, Social network service, Melatonin


Insufficient sleep is associated with obesity, yet little is known about how repeated nights of insufficient sleep influence energy expenditure and balance. We studied 16 adults in a 14- to 15-d-long inpatient study and quantified effects of 5 d of insufficient sleep, equivalent to a work week, on energy expenditure and energy intake compared with adequate sleep. We found that insufficient sleep increased total daily energy expenditure by ∼5%; however, energy intake-especially at night after dinner-was in excess of energy needed to maintain energy balance. Insufficient sleep led to 0.82 ± 0.47 kg (±SD) weight gain despite changes in hunger and satiety hormones ghrelin and leptin, and peptide YY, which signaled excess energy stores. Insufficient sleep delayed circadian melatonin phase and also led to an earlier circadian phase of wake time. Sex differences showed women, not men, maintained weight during adequate sleep, whereas insufficient sleep reduced dietary restraint and led to weight gain in women. Our findings suggest that increased food intake during insufficient sleep is a physiological adaptation to provide energy needed to sustain additional wakefulness; yet when food is easily accessible, intake surpasses that needed. We also found that transitioning from an insufficient to adequate/recovery sleep schedule decreased energy intake, especially of fats and carbohydrates, and led to -0.03 ± 0.50 kg weight loss. These findings provide evidence that sleep plays a key role in energy metabolism. Importantly, they demonstrate physiological and behavioral mechanisms by which insufficient sleep may contribute to overweight and obesity.

Concepts: Metabolism, Nutrition, Obesity, Mass, Dieting, Circadian rhythm, Appetite, Melatonin


Patterns of daily human activity are controlled by an intrinsic circadian clock that promotes ∼24 hr rhythms in many behavioral and physiological processes. This system is altered in delayed sleep phase disorder (DSPD), a common form of insomnia in which sleep episodes are shifted to later times misaligned with the societal norm. Here, we report a hereditary form of DSPD associated with a dominant coding variation in the core circadian clock gene CRY1, which creates a transcriptional inhibitor with enhanced affinity for circadian activator proteins Clock and Bmal1. This gain-of-function CRY1 variant causes reduced expression of key transcriptional targets and lengthens the period of circadian molecular rhythms, providing a mechanistic link to DSPD symptoms. The allele has a frequency of up to 0.6%, and reverse phenotyping of unrelated families corroborates late and/or fragmented sleep patterns in carriers, suggesting that it affects sleep behavior in a sizeable portion of the human population.

Concepts: Gene, Evolution, Sleep disorder, Circadian rhythm, ARNTL, Delayed sleep phase syndrome, Melatonin, Advanced sleep phase syndrome