Caffeine's wakefulness-promoting and sleep-disrupting effects are well established, yet whether caffeine affects human circadian timing is unknown. We show that evening caffeine consumption delays ...the human circadian melatonin rhythm in vivo and that chronic application of caffeine lengthens the circadian period of molecular oscillations in vitro, primarily with an adenosine receptor/cyclic adenosine monophosphate (AMP)-dependent mechanism. In a double-blind, placebo-controlled, ~49-day long, within-subject study, we found that consumption of a caffeine dose equivalent to that in a double espresso 3 hours before habitual bedtime induced a ~40-min phase delay of the circadian melatonin rhythm in humans. This magnitude of delay was nearly half of the magnitude of the phase-delaying response induced by exposure to 3 hours of evening bright light (~3000 lux, ~7 W/m(2)) that began at habitual bedtime. Furthermore, using human osteosarcoma U2OS cells expressing clock gene luciferase reporters, we found a dose-dependent lengthening of the circadian period by caffeine. By pharmacological dissection and small interfering RNA knockdown, we established that perturbation of adenosine receptor signaling, but not ryanodine receptor or phosphodiesterase activity, was sufficient to account for caffeine's effects on cellular timekeeping. We also used a cyclic AMP biosensor to show that caffeine increased cyclic AMP levels, indicating that caffeine influenced a core component of the cellular circadian clock. Together, our findings demonstrate that caffeine influences human circadian timing, showing one way that the world's most widely consumed psychoactive drug affects human physiology.
Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by ...assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure.
Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (∼1.9 lux, ∼0.6 Watts/m(2))-placebo, dim light-melatonin (5 mg), bright light (∼3000 lux, ∼7 Watts/m(2))-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time.
Sleep and chronobiology laboratory environment free of time cues.
Thirty-six healthy participants (18 females) aged 22 ± 4 y (mean ± SD).
Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances.
Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders.
Summary
Sleep inertia is affected by circadian phase, with worse performance upon awakening from sleep during the biological night than biological day. Visual search/selective visual attention ...performance is known to be sensitive to sleep inertia and circadian phase. Individual differences exist in the circadian timing of habitual wake time, which may contribute to individual differences in sleep inertia. Because later chronotypes awaken at an earlier circadian phase, we hypothesized that later chronotypes would have worse visual search performance during sleep inertia than earlier chronotypes if awakened at habitual wake time. We analysed performance from 18 healthy participants five females (22.1 ± 3.7 years; mean ± SD) at ~1, 10, 20, 30, 40 and 60 min following electroencephalogram‐verified awakening from an 8 h in‐laboratory sleep opportunity. Cognitive throughput and reaction times of correct responses were impaired by sleep inertia and took ~10–30 min to improve after awakening. Regardless whether chronotype was defined by dim light melatonin onset or mid‐sleep clock hour on free days, derived from the Munich ChronoType Questionnaire, the duration of sleep inertia for cognitive throughput and reaction times was longer for later chronotypes (n = 7) compared with earlier chronotypes (n = 7). Specifically, performance for earlier chronotypes showed significant improvement within ~10–20 min after awakening, whereas performance for later chronotypes took ~30 min or longer to show significant improvement (P < 0.05). Findings have implications for decision making immediately upon awakening from sleep, and are consistent with circadian theory suggesting that sleep inertia contributes to longer‐lasting impairments in morning performance in later chronotypes.
Musculoskeletal injuries (MSKIs) are a significant health problem in the military. Accordingly, identifying risk factors associated with MSKI to develop targeted strategies that attenuate injury risk ...remains a top priority within the military. Insufficient sleep has garnered increased attention as a potential risk factor for MSKI in both civilians and military personnel. Yet, there are no systematic evaluations of the potential association between sleep and MSKI in the military. The purpose of this review is to examine the relationship between sleep and injury in military personnel.
Literature searches were performed in multiple electronic databases using keywords relevant to sleep quantity and quality, MSKI, and military populations. Two investigators independently assessed the methodological quality of each study using the Newcastle-Ottawa Scale for cohort studies or an adapted form of this scale for cross-sectional studies.
The search yielded 2402 total citations, with 8 studies (3 cohort and 5 cross-sectional) fitting the inclusion criteria. Overall, the systematic review found 5 of the 8 reviewed studies supporting an association between sleep (quality and duration) and MSKI in military personnel. Specifically, poor sleep was associated with increased injury incidence in 2 cohort and 3 cross-sectional studies.
This is the first systematic review to evaluate the published literature on the association between sleep and MSKI risk in military populations. Although there is currently limited research on this topic, findings suggest that sleep is associated with MSKI and should be considered when designing strategies aimed at reducing MSKI risk in military personnel.
Abstract
Experimental sleep restriction and deprivation lead to risky decision-making. Further, in naturalistic settings, short sleep duration and poor sleep quality have been linked to real-world ...high-risk behaviors (HRB), such as reckless driving or substance use. Military populations, in general, tend to sleep less and have poorer sleep quality than nonmilitary populations due to a number of occupational, cultural, and psychosocial factors (e.g. continuous operations, stress, and trauma). Consequently, it is possible that insufficient sleep in this population is linked to HRB. To investigate this question, we combined data from four diverse United States Army samples and conducted a mega-analysis by aggregating raw, individual-level data (n = 2,296, age 24.7 ± 5.3). A negative binomial regression and a logistic regression were used to determine whether subjective sleep quality (Pittsburgh Sleep Quality Index PSQI, Insomnia Severity Index ISI, and duration h) predicted instances of military-specific HRB and the commission of any HRB (yes/no), respectively. Poor sleep quality slightly elevated the risk for committing HRBs (PSQI Exp(B): 1.12 and ISI Exp(B): 1.07), and longer duration reduced the risk for HRBs to a greater extent (Exp(B): 0.78), even when controlling for a number of relevant demographic factors. Longer sleep duration also predicted a decreased risk for commission of any HRB behaviors (Exp(B): 0.71). These findings demonstrate that sleep quality and duration (the latter factor, in particular) could be targets for reducing excessive HRB in military populations. These findings could therefore lead to unit-wide or military-wide policy changes regarding sleep and HRB.
There are replicable inter-individual differences in cognitive responsivity to sleep loss. Genetic allele variations have been linked with behavioral differences in cognitive performance under these ...conditions, yet less burdensome tests or screeners are not available. This study tested whether a survey can classify U.S. Army Soldiers as cognitively vulnerable or resilient to sleep loss and whether Soldiers in these differentiated groups have the expected allele variants. Six genetic targets were sequenced from 75 Soldiers. Cognition was tested after a night of total sleep deprivation during a military exercise. The Iowa Resilience to Sleeplessness Test (iREST) was administered. A Wilcoxon Rank Sum test showed the iREST score of 2.5/5 differentiated groups behaviorally on all cognitive tests. Chi-squared tests showed that for the Catechol-O-Methyltransferase (COMT) gene, 82% of behaviorally vulnerable soldiers had alleles linked with vulnerability, compared with 41% of behaviorally genetic soldiers. If these findings are replicated, the iREST could be used to help military leaders make decisions about personnel placement when sleep loss is unavoidable.
Burke, TM, Lisman, PJ, Maguire, K, Skeiky, L, Choynowski, JJ, CapaldiII, VF, Wilder, JN, Brager, AJ, and Dobrosielski, DA. Examination of sleep and injury among college football athletes. J Strength ...Cond Res 34(3): 609-616, 2020-The purpose of this study was to characterize subjective sleep metrics in collegiate football players at the start of the season, determine the relationship between preseason subjective sleep measures and in-season objective sleep characteristics, and examine the association between subjective and objective sleep metrics and incidence of time-loss injury during the competitive season. Ninety-four Division I football players completed 5 validated sleep-related questionnaires to assess sleep quality, insomnia severity, daytime sleepiness, sleep apnea risk, and circadian preference before the start of the season. Clinical thresholds for sleep questionnaires were used to determine risk of sleep disorders. Continuous wrist actigraphy was collected throughout the season to generalize sleep behaviors. Time-loss injury incidence data were recorded and used for analysis. Results indicated that 67.4% (60 of 89) of athletes scored above clinical threshold in at least 1 questionnaire to indicate sleep disorder risk. At the start of the season, players subjectively reported an average sleep duration of 7:16 ± 1:18 hours:minutes, which was in contrast to the 6:04 ± 0:41 hours:minutes measured through actigraphy during the season. Logistic regression models adjusted for age and body mass index revealed no significant associations between injury and subjective (odds ratio OR = 1.00; 95% confidence interval CI = 0.99-1.01) and objective (OR = 1.01; 95% CI = 0.99-1.02) sleep duration or measures attained from sleep questionnaires (ORs ranged from 1.01 to 2.87). Sleep metrics (quantity and quality) were not associated with increased risk of injury in this cohort of collegiate football players.
Determine stability of individual differences in executive function, cognitive processing speed, selective visual attention, and maintenance of wakefulness during simulated sustained operations with ...combined sleep restriction and circadian misalignment.
Twenty healthy adults (eight female), aged 25.7 (±4.2 SD), body mass index (BMI) 22.3 (±2.1) kg/m2 completed an 18-day protocol twice. Participants maintained habitual self-selected 8-hour sleep schedules for 2 weeks at home prior to a 4-day laboratory visit that included one sleep opportunity per day: 8 hours on night 1, 3 hours on night 2, and 3 hours on mornings 3 and 4. After 3 days of unscheduled sleep at home, participants repeated the entire protocol. Stability and task dependency of individual differences in performance were quantified by intra-class correlation coefficients (ICC) and Kendall's Tau, respectively.
Performance on Stroop, Visual Search, and the Maintenance of Wakefulness Test were highly consistent within individuals during combined sleep restriction and circadian misalignment. Individual differences were trait-like as indicated by ICCs (0.54-0.96) classified according to standard criteria as moderate to almost perfect. Individual differences on other performance tasks commonly reported in sleep studies showed fair to almost perfect ICCs (0.22-0.94). Kendall's rank correlations showed that individual vulnerability to sleep restriction and circadian misalignment varied by task and by metric within a task.
Consistent vulnerability of higher-order cognition and maintenance of wakefulness to combined sleep restriction and circadian misalignment has implications for the development of precision countermeasure strategies for workers performing safety-critical tasks, e.g. military, police, health care workers and emergency responders.
ABSTRACT
Introduction
Musculoskeletal injuries and insufficient sleep are common among U.S. Army Rangers. There has been limited research into whether indices of sleep differ between injured and ...uninjured Rangers. The purpose of this study was to investigate the association between self-reported sleep and musculoskeletal injury in Rangers.
Materials and Methods
A total of 82 Army Rangers (male, 25.4 ± 4.0 years) were asked if they currently have any musculoskeletal injuries; completed the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), and the Stanford Sleepiness Scale; and were asked about their average sleep quality/sleep duration over the preceding week. Rangers were then dichotomized into groups, one that reported a current musculoskeletal injury and another that did not.
Results
The reported musculoskeletal injury prevalence was 15.9% (n = 13). The Rangers that reported an injury, compared to those that did not, had a significantly higher Global PSQI score (6.7 ± 3.7 versus 4.5 ± 2.7, P = .012) and ISI score (10.9 ± 3.7 versus 7.2 ± 4.1, P = .003), both indicative of poorer sleep. The group reporting an injury rated their average sleep quality over the preceding week significantly lower compared to those that did not report an injury (50.8 ± 17.5 versus 68.9 ± 18.3, P = .001). There was no significant group difference in the average nightly sleep duration (6.1 ± 1.0 hours versus 6.5 ± 0.9 hours, P = .099).
Conclusion
In this cohort of male Army Rangers, In this cohort of male Army Rangers, those with a musculoskeletal injury reported poorer sleep quality than uninjured Rangers. Sleep duration was not associated with reported injuries; however, both the injured group and uninjured group averaged less than the recommended amounts of sleep. Further investigation into the relationship between musculoskeletal injury and sleep in military personnel is warranted.
It is widely established that insufficient sleep can lead to adverse health outcomes. Paradoxically, epidemiologic research suggests that individuals who report habitual nightly sleep greater than ...9 h also are at risk for adverse health outcomes. Further, studies have shown that long sleepers have decreased activity levels, which may partially explain the relationship between long sleep duration and mortality. The influence of sleep extension (longer time in bed) on levels of daily activity has not yet been established. The current study examined whether a week of sleep extension altered activity levels within the subsequent daily waking active and sleep period in order to determine whether increased time in bed indeed is related to decreased activity levels.
A total of 26 healthy volunteers wore wrist accelerometer devices (Actiwatch 2.0, Philips) in order to objectively measure sleep and activity for six days during their normal schedules and for six days during a sleep extension (10 h time in bed) intervention.
There were no significant or clinically-relevant differences in 24-h activity or activity during the active or sleep period between baseline and sleep extension conditions. There were no main or interaction effects of day and condition when daily activity counts were compared between baseline and sleep extension conditions for the 24 h period (Day: F(5, 21) = 1.92, p = 0.12; Condition: F(1,25) = 2.93, p = 0.09; Day by Condition: F(5,21) = 0.32, p = 0.83), Active Waking Period (Day: F(5,25) = 1.53, p = 0.18; Condition: F(1,25) = 0.26, p = 0.61; Day by Condition: F(5,21) = 0.55, p = 0.74) or Nightly Sleep (Day: F(5,21) = 0.86, p = 0.51; Condition: F(1,25) = 1.78, p = 0.19; Day by Condition: F(5,21) = 0.79, p = 0.56) periods. In contrast, there was a main effect of condition when examining sleep duration by day between conditions (Day: F(5,21) = 1.60, p = 0.16; Condition: F(1,25) = 167.31, p < 0.001; Day by Condition: F(5,21) = 2.31, p = 0.07), such that sleep duration was longer during the sleep extension condition.
Sleep duration increased during six days of a sleep extension protocol but activity levels remained similar to their baseline (normal) sleep schedule. The current findings suggest that extending time in bed alone does not alter waking activity counts in young healthy adults. The link between extended sleep and adverse health outcomes may be attributable to other phenotypic factors, or other biological correlates of extended sleep and poor health.
•Sleep extension increased sleep duration in healthy sleeping adults.•Sleep extension was not related to a decrease in actigraphy-measured activity levels.•Sedentary activity (NHANES cutoff; AC/min<100) was reduced during sleep extension.