Timing of Sleep and Its Relationship with the Endogenous Melatonin Rhythm

While much research has investigated the effects of exogenous melatonin on sleep, less is known about the relationship between the timing of the endogenous melatonin rhythm and the sleep–wake cycle. Significant inter-individual variability in the phase relationship between sleep and melatonin rhythms has been reported although the extent to which the variability reflects intrinsic and/or environmental differences is unknown. We examined the effects of different sleeping schedules on the time of dim light melatonin onset (DLMO) in 28 young, healthy adults. Participants chose to maintain either an early (22:30–06:30 h) or a late (00:30–08:30 h) sleep schedule for at least 3 weeks prior to an overnight laboratory visit. Saliva samples were collected under dim light (<2 lux) and controlled posture conditions to determine salivary DLMO. The 2-h difference between groups in the enforced sleep–wake schedule was associated with a concomitant 1.75-h delay in DLMO. The mean phase relationship between sleep onset and DLMO remained constant (~2 h). The variance in DLMO time, however, was greater in the late group (range 4.5 h) compared to the early group (range 2.4 h) perhaps due to greater effect of environmental influences in delayed sleep types or greater intrinsic instability in their circadian system. The findings contribute to our understanding of individual differences in the human circadian clock and have important implications for the diagnosis and treatment of circadian rhythm sleep disorders, in particular if a greater normative range for phase angle of entrainment occurs in individuals with later sleep–wake schedules

Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase

Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01), greater sleepiness (r = 0.510, p < 0.0001), and more slow eye movements (r = 0.375, p = 0.022) were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual’s circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation

Long-haul pilots use in-flight napping as a countermeasure to fatigue

The aim of this study was to examine the effects of fatigue on the amount of in-flight sleep obtained by airline pilots during long-haul duty periods. A total of 301 pilots collected sleep/wake and work/rest data for a period of at least 2 weeks each. Fatigue likelihood, i.e. low, moderate, high, or extreme, was estimated for each duty period based on a pilot’s sleep/wake behaviour prior to duty and the time of day that the duty period occurred. Participants obtained 1.8 h of sleep (i.e. 27% of their rest time) during duty periods with low fatigue likelihood and 3.7 h of sleep (i.e. 54% of their rest time) during duty periods with extreme fatigue likelihood. These results indicate that (i) long-haul pilots obtain substantially more sleep during duty periods when fatigue is likely to be extreme than when fatigue is likely to be low and (ii) long-haul pilots use in-flight napping as a fatigue countermeasure, but more could be done to increase its efficacy.

Blue-light phase shifts PER3 gene expression in human leukocytes

The timing of clock gene expression in human leukocytes was investigated following a phase-advancing light stimulus to determine whether the response is wavelength- and/or age-dependent. PERIOD3 (PER3) clock gene expression in leukocytes and plasma melatonin were analyzed before and after monochromatic blue and green light exposure. Significant phase advances were observed in the peak timing of both PER3 expression and melatonin following blue but not green light. The amplitude of the PER3 rhythm at baseline was significantly reduced with age. However, age did not affect the response of the PER3 rhythm to light.</p

Efficacy of melatonin for sleep disturbance following traumatic brain injury: a randomised controlled trial

Abstract Background The study aimed to determine the efficacy of melatonin supplementation for sleep disturbances in patients with traumatic brain injury (TBI). Methods This is a randomised double-blind placebo-controlled two-period two-treatment (melatonin and placebo) crossover study. Outpatients were recruited from Epworth and Austin Hospitals Melbourne, Australia. They had mild to severe TBI (n = 33) reporting sleep disturbances post-injury (mean age 37 years, standard deviation 11 years; 67% men). They were given prolonged-release melatonin formulation (2 mg; Circadin®) and placebo capsules for 4 weeks each in a counterbalanced fashion separated by a 48-hour washout period. Treatment was taken nightly 2 hours before bedtime. Serious adverse events and side-effects were monitored. Results Melatonin supplementation significantly reduced global Pittsburgh Sleep Quality Index scores relative to placebo, indicating improved sleep quality [melatonin 7.68 vs. placebo 9.47, original score units; difference -1.79; 95% confidence interval (CI), -2.70 to -0.88; p ≤ 0.0001]. Melatonin had no effect on sleep onset latency (melatonin 1.37 vs. placebo 1.42, log units; difference -0.05; 95% CI, -0.14 to 0.03; p = 0.23). With respect to the secondary outcomes, melatonin supplementation increased sleep efficiency on actigraphy, and vitality and mental health on the SF-36 v1 questionnaire (p ≤ 0.05 for each). Melatonin decreased anxiety on the Hospital Anxiety Depression Scale and fatigue on the Fatigue Severity Scale (p ≤ 0.05 for both), but had no significant effect on daytime sleepiness on the Epworth Sleepiness Scale (p = 0.15). No serious adverse events were reported. Conclusions Melatonin supplementation over a 4-week period is effective and safe in improving subjective sleep quality as well as some aspects of objective sleep quality in patients with TBI. Trial registration Identifier: 12611000734965; Prospectively registered on 13 July 2011

The ability to self-monitor cognitive performance during 60 h total sleep deprivation and following 2 nights recovery sleep

We aimed to investigate whether self-monitoring of performance is altered during 60 h of total sleep deprivation, following 2 nights of recovery sleep, and by task difficulty and/or subjective sleepiness. Forty adults (22 females, aged 19-39 years) underwent a 5-day protocol, with a well-rested day, 66 h total sleep deprivation (last test session at 60 h), and 2 nights of 8 h recovery sleep. An arithmetic task (MATH) with three difficulty levels assessed working memory. The Psychomotor Vigilance Task assessed sustained attention. Arithmetic accuracy and Psychomotor Vigilance Task median reaction time measured objective performance. Subjective performance was measured with self-reported accuracy and speed. Objective-subjective differences assessed self-monitoring ability. The performance on both tasks declined during total sleep deprivation and improved following recovery. During total sleep deprivation, participants accurately self-monitored performance on the Psychomotor Vigilance Task; however, they overestimated cognitive deficits on MATH, self-reporting performance as worse than actually observed. Following recovery, participants overestimated the extent of performance improvement on the Psychomotor Vigilance Task. Task difficulty influenced self-monitoring ability, with greater overestimation of performance deficits during total sleep deprivation as difficulty increased. Subjective sleepiness predicted subjective performance ratings at several time points, only for the Psychomotor Vigilance Task. The ability to self-monitor performance was impaired during total sleep deprivation for working memory and after recovery sleep for the Psychomotor Vigilance Task, but was otherwise accurate. The development of self-monitoring strategies, assessing both subjective perceptions of performance and subjective sleepiness, within operational contexts may help reduce the consequences of sleep-related impairments

Age-dependent alterations in human PER2 levels after early morning blue light exposure

In our modern society, we are exposed to different artificial light sources that could potentially lead to disturbances of circadian rhythms and, hence, represent a risk for health and welfare. Investigating the acute impact of light on clock-gene expression may thus help us to better understand the mechanisms underlying disorders rooted in the circadian system. Here, we show an overall significant reduction in PER2 expression in oral mucosa with aging in the morning, noon, and afternoon. In the afternoon, 10 h after exposure to early morning blue light, PER2 was significantly elevated in the young compared to green light exposure and to older participants. Our findings demonstrate that human buccal samples are a valuable tool for studying clock-gene rhythms and the response of PER2 to light. Additionally, our results indicate that the influence of light on clock-gene expression in humans is altered with age

Genetic and environmental contributions to sleep-wake behavior in 12-year-old twins

Study Objectives: To examine the role of genetic and environmental factors on sleep behavior in 12-year-old twins matched for family environment