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Numerous studies have reported that eveningness is associated with increased alcohol consumption. However, biological markers of circadian timing, such as dim light melatonin onset (DLMO) and circadian photoreceptor responsivity (post-illumination pupil response, PIPR), have rarely been assessed in the context of habitual alcohol consumption. This study aimed to examine sleep, circadian timing, and photoreceptor responsivity in adult alcohol drinkers.Participants (21 to 45 years) included 28 light and 50 heavy drinkers. The 8-day study consisted of a week of ad lib sleep monitored with wrist actigraphy, followed by a 9-h laboratory session with a photoreceptor responsivity and circadian phase assessment.The heavy drinkers obtained on average 28 more minutes of sleep (p = 0.002) and reported more eveningness than the light drinkers (p = 0.029). There was a trend for a shorter DLMO-midsleep interval (p = 0.059) in the heavy drinkers, reflecting a tendency for them to sleep at an earlier circadian phase. The PIPR in the heavy drinkers was significantly smaller than in the light drinkers (p = 0.032), suggesting reduced circadian photoreceptor responsivity in the heavy drinkers. A larger PIPR was significantly associated with a later DLMO in the light drinkers (r = 0.44, p = 0.019), but this relationship was absent in the heavy drinkers (r = -0.01, p = 0.94).These results are consistent with earlier reports of more eveningness and a shorter DLMO-midsleep interval being associated with heavier alcohol drinking. The novel finding of reduced circadian photoreceptor responsivity in heavy drinkers is consistent with prior rodent studies. Future studies should explore the impact of habitual alcohol consumption on other measures of circadian photoreceptor responsivity.

BACKGROUND: Sleep disturbance is common among individuals with Tourette’s Disorder (TD). Given that sleep is influenced by the circadian system, this study examined circadian rhythms and sleep in adults with TD, and explored the possible benefit of short-wavelength wearable morning light therapy. METHODS: Participants were 34 adults with TD (n=14) and age- and sex-matched healthy controls (HC; n=20). Participants were screened using clinician-rated diagnostic and tic severity interviews, and procedures lasted 3 consecutive weeks. Participants completed a baseline week of actigraphy. Adults with TD completed two weeks of Re-Timer(™) morning light therapy and continued actigraphy monitoring. Dim light melatonin onset (DLMO) phase assessment, tic severity interview, and measures of chronotype, sleep disturbance, daytime sleepiness, disability, depression, anxiety, and stress were completed at baseline and post-intervention. RESULTS: Adults with TD reported significantly greater eveningness and sleep disturbance relative to controls. Per wrist actigraphy, adults with TD exhibited significantly longer sleep onset latency, lower sleep efficiency, and greater sleep fragmentation than HC. Following morning light therapy there was significant advances in DLMO phase, but not self-report or actigraphy sleep variables. There were small, statistically significant decreases in tic severity and impairment. There were also significant reductions in daytime sleepiness, and self-reported anxiety, but not depression, stress, or disability. Participants reported minimal side effects and rated light therapy as acceptable and comfortable. CONCLUSIONS: Findings showed some benefits following brief light therapy in TD; further exploration of the impact of spectral tuning the photic environment as part of treatment for TD subjects is warranted.

Light is a potent circadian entraining agent. For many people, daily light exposure is fundamentally dysregulated with reduced light during the day and increased light into the late evening. This lighting schedule promotes chronic disruption to circadian physiology resulting in a myriad of impairments. Developmental changes in sleep-wake physiology suggest that such light exposure patterns may be particularly disruptive for adolescents and further compounded by lifestyle factors such as early school start times. This narrative review describes evidence that reduced light exposure during the school day delays the circadian clock, and longer exposure durations to light-emitting electronic devices in the evening suppress melatonin. While home lighting in the evening can suppress melatonin secretion and delay circadian phase, the patterning of light exposure across the day and evening can have moderating effects. Photic countermeasures may be flexibly and scalably implemented to support sleep-wake health; including manipulations of light intensity, spectra, duration and delivery modality across multiple contexts. An integrative approach addressing physiology, attitudes, and behaviors will support optimization of light-driven sleep-wake outcomes in adolescents.

This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep–wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.

Study ObjectivesA critical barrier to successful treatment of circadian misalignment in shift workers is determining circadian phase in a clinical or field setting. Light and movement data collected passively from wrist actigraphy can generate predictions of circadian phase via mathematical models; however, these models have largely been tested in non-shift working adults. This study tested the feasibility and accuracy of actigraphy in predicting dim light melatonin onset (DLMO) in fixed night shift workers.MethodsA sample of 45 night shift workers wore wrist actigraphs before completing DLMO in the laboratory (17.0 days ± 10.3 SD). DLMO was assessed via 24 hourly saliva samples in dim light (ResultsModel predictions of DLMO showed good concordance with in-lab DLMO, with Lin’s concordance coefficient of 0.70, which was twice as high as agreement using average sleep timing as a proxy of DLMO. The absolute mean error of the predictions was 2.88 h, with 76% and 91% of the predictions falling with 2 and 4 h, respectively.ConclusionThis study is the first to demonstrate the use of wrist actigraphy-based estimates of circadian phase as a clinically useful and valid alternative to in-lab measurement of DLMO in fixed night shift workers. Future research should explore how additional predictors may impact accuracy.

Study Objectives We investigated biological and behavioral rhythm period lengths (i.e. taus) of delayed sleep–wake phase disorder (DSWPD) and non-24-hour sleep–wake rhythm disorder (N24SWD). Based on circadian phase timing (temperature and dim light melatonin onset), DSWPD participants were dichotomized into a circadian-delayed and a circadian non-delayed group to investigate etiological differences. Methods Participants with DSWPD (n = 26, 17 m, age: 21.85 ± 4.97 years), full-sighted N24SWD (n = 4, 3 m, age: 25.75 ± 4.99 years) and 18 controls (10 m, age: 23.72 ± 5.10 years) participated in an 80-h modified constant routine. An ultradian protocol of 1-h “days” in dim light, controlled conditions alternated 20-min sleep/dark periods with 40-min enforced wakefulness/light. Subjective sleepiness ratings were recorded prior to every sleep/dark opportunity and median reaction time (vigilance) was measured hourly. Obtained sleep (sleep propensity) was derived from 20-min sleep/dark opportunities to quantify hourly objective sleepiness. Hourly core body temperature was recorded, and salivary melatonin assayed to measure endogenous circadian rhythms. Rhythm data were curved using the two-component cosine model. Results Patients with DSWPD and N24SWD had significantly longer melatonin and temperature taus compared to controls. Circadian non-delayed DSWPD had normally timed temperature and melatonin rhythms but were typically sleeping at relatively late circadian phases compared to those with circadian-delayed DSWPD. Conclusions People with DSWPD and N24SWD exhibit significantly longer biological circadian rhythm period lengths compared to controls. Approximately half of those diagnosed with DSWPD do not have abnormally delayed circadian rhythm timings suggesting abnormal phase relationship between biological rhythms and behavioral sleep period or potentially conditioned sleep-onset insomnia.

OBJECTIVE: To examine the feasibility, acceptability, and effects of a home-based morning bright light treatment on pain, mood, sleep, and circadian timing in US veterans with chronic low back pain. DESIGN: An open treatment trial with a seven-day baseline, followed by 13 days of a one-hour morning bright light treatment self-administered at home. Pain, pain sensitivity, mood, sleep, and circadian timing were assessed before, during, and after treatment. SETTING: Participants slept at home, with weekly study visits and home saliva collections. PARTICIPANTS: Thirty-seven US veterans with medically verified chronic low back pain. METHODS: Pain, mood, and sleep quality were assessed with questionnaires. Pain sensitivity was assessed using two laboratory tasks: a heat stimulus and an ischemia stimulus that gave measures of threshold and tolerance. Sleep was objectively assessed with wrist actigraphy. Circadian timing was assessed with the dim light melatonin onset. RESULTS: Morning bright light treatment led to reduced pain intensity, pain behavior, thermal pain threshold sensitivity, post-traumatic stress disorder symptoms, and improved sleep quality (P

ᅟ The Morningness-Eveningness Questionnaire (MEQ) and Munich ChronoType Questionnaire (MCTQ) are sometimes used to estimate circadian timing. However, it remains unclear if they can reflect a change in circadian timing after a light treatment. In this study, 31 participants (25–68 years) completed both questionnaires before and after a 13–28 day morning light treatment. The dim light melatonin onset (DLMO), a physiological marker of circadian timing, was also assessed in a subsample of 16 participants. The DLMO phase advanced on average by 47 min (p

This article focuses on melatonin and other melatonin receptor agonists, and specifically their circadian phase shifting and sleep-enhancing properties. The circadian system and circadian rhythm sleep-wake disorders are briefly reviewed, followed by a summary of the circadian phase shifting, sleep-enhancing properties, and possible safety concerns associated with melatonin and other melatonin receptor agonists. The recommended use of melatonin, including dose and timing, in the latest American Academy of Sleep Medicine Clinical Practice Guidelines for the treatment of intrinsic circadian rhythm disorders is also reviewed. Lastly, the practical aspects of treatment and consideration of clinical treatment outcomes are discussed.

Objective This observational pilot study examined objective circadian phase and sleep timing in chronic migraine (CM) and healthy controls (HC) and the impact of circadian factors on migraine frequency and severity. Background Sleep disturbance has been identified as a risk factor in the development and maintenance of CM but the biological mechanisms linking sleep and migraine remain largely theoretical. Methods Twenty women with CM and 20 age-matched HC completed a protocol that included a 7 day sleep assessment at home using wrist actigraphy followed by a circadian phase assessment using salivary melatonin. We compared CM vs HC on sleep parameters and circadian factors. Subsequently, we examined associations between dim-light melatonin onset (DLMO), the midpoint of the sleep episode, and the phase angle (time from DLMO to sleep midpoint) with the number of migraine days per month and the migraine disability assessment scale (MIDAS). Results CM and HC did not differ on measures of sleep or circadian phase. Within the CM group, more frequent migraine days per month was significantly correlated with DLMO (r = .49, P = .039) and later sleep episode (r = .47, P = .037). In addition, a greater phase angle (ie, circadian misalignment) was significantly correlated with more severe migraine-related disability (r = .48, P = .042). These relationships remained significant after adjusting for total sleep time. Conclusions This pilot study revealed that circadian misalignment and delayed sleep timing are associated with higher migraine frequency and severity, which was not better accounted for by the amount of sleep. These findings support the plausibility and need for further investigation of a circadian pathway in the development and maintenance of chronic headaches. Specifically, circadian misalignment and delayed sleep timing could serve as an exacerbating factor in chronic migraines when combined with biological predispositions or environmental factors.

Few studies have examined relationships between circadian rhythms and unipolar major depressive disorder. Further, no study to date has examined circadian markers as predictors of response to depression treatment. In the present study, we examined associations between circadian timing and its alignment with sleep and depression severity in 30 adults with major depressive disorder who completed a randomized controlled trial of two weeks of time in bed (TIB) restriction administered adjunctive to fluoxetine, with a focus on sex differences. Thirty adults with major depressive disorder received 8 weeks of fluoxetine 20–40 mgs and were randomized to 8h TIB or 6h TIB for the first 2 weeks. Participants in the 6h TIB condition were further randomized to a delayed bedtime or advanced risetime group. Circadian measures included dim light melatonin onset (DLMO) and the difference between DLMO and midsleep point (i.e., phase angle difference). Depression was assessed using the Hamilton Rating Scale for Depression. For females, a phase delay after 2 weeks of fluoxetine and the experimental TIB manipulation was associated with a poorer response to fluoxetine, and depression severity was negatively correlated with phase angle difference, whereas males showed a positive correlation between depression severity and phase angle difference.

Citation:Goldstein CA, Burgess HJ. Hit or miss: the use of melatonin supplements. J Clin Sleep Med. 2020;16(suppl_1):29S–30S.

Introduction Delayed sleep-wake phase disorder (DSWPD) is common, debilitating, and challenging to treat. In an ongoing randomized trial, we are comparing exogenous melatonin treatment outcomes in DSWPD participants for whom dim light melatonin onset (DLMO) is measured objectively vs. estimated. Methods Thus far, 13 participants (27±6 years old, 67% female) have completed a randomized, controlled, double-blind 4-week trial of 0.5 mg of exogenous melatonin timed to either 3 h before measured DLMO (M-DLMO, n = 6) or 3 h before DLMO estimated at 2 h before average sleep onset time based on at least 7 days of wrist actigraphy and sleep diary (E-DLMO, n = 7). All participants met International Classification of Sleep Disorders-3 diagnostic criteria for DSWPD and were otherwise healthy. Participants completed 4 weekly treatment sessions with a blinded psychologist; time of melatonin administration and bed-rise schedule were advanced up to 1 h/week. A validated home saliva collection kit measured DLMO in all participants. Between-group t-tests and Hedges’ g effect sizes (ES) were calculated at post-treatment for the following outcomes: DLMO; Pittsburgh Sleep Quality Index (PSQI) global score; Morningness-Eveningness Questionnaire (MEQ); and the actigraphy parameters sleep efficiency (SE) and clock time of sleep onset and offset. A paired-sample t-test compared the measured vs. estimated DLMO at baseline. Results The M-DLMO group had a 65±88 mins DLMO advance vs. 27±30 mins in the E-DLMO group (ES=0.51 p=.381). PSQI scores were similar between groups (M-DLMO=6.67±2.06, E-DLMO=7.1± 1.57, ES=-0.24, p=.646), as were MEQ scores (M-DLMO=43±4.98, E-DLMO=48±12.72, ES=-0.47, p=.387). Sleep onset time (M-DLMO=0:32±1:02, E-DLMO=0:31±1:38, ES=0.01, p=.98) and offset time (M-DLMO=8:05±1:03, E-DLMO=8:08±2:14, ES=-0.02, p=.968) were similar between the groups, although sleep was more efficient in M-DLMO vs. E-DLMO (84%±3% vs. 76%±10%, ES=0.94, p=.096). On average, baseline measured DLMO occurred 123±83 mins earlier than estimated DLMO (p=.001). Conclusion We are continuing to enroll participants in this trial. Preliminary results suggest some potential benefit of measuring the DLMO, but results will need to be clarified in a larger sample. Support American Sleep Medicine Foundation Strategic Research Award

The dim light melatonin onset (DLMO) is the most reliable measure of central circadian timing in humans. However, it is not always possible to measure the DLMO because sample collection has to occur in the hours before usual sleep onset, it requires staff support and considerable participant effort, and it is relatively expensive. Questionnaires that ask people about the timing of their behavior, such as their sleep, may provide an easier and less expensive estimate of circadian timing. The objective of this analysis was to compare the MEQ score derived from the Morningness-Eveningness Questionnaire (MEQ) and the MSFsc derived from the Munich ChronoType Questionnaire (MCTQ) to the DLMO in the largest sample to date ( N = 60). Our hypothesis was that MSFsc would correlate more highly with the DLMO than MEQ score. Our sample of 36 healthy controls and 24 patients with delayed sleep phase disorder ranged in age from 18 to 62 years. All participants slept at times of their own choosing for a week before the assessment of their DLMO. The DLMO correlated significantly with both the MEQ score ( r = −0.70, p < 0.001) and MSFsc ( r = 0.68, p < 0.001). A linear regression using MEQ, MSFsc, and age to predict the DLMO explained 60% of the DLMO variance. The strongest predictor of the DLMO was MSFsc (beta = 0.51, p = 0.001), followed by MEQ (beta = −0.41, p = 0.004), and age (beta = 0.26, p = 0.013). The beta values for MSFsc and MEQ score were not statistically different from each other. Nonetheless, around a 4-h range in the DLMO was observed at a given MEQ score and a given MSFsc, indicating that neither questionnaire should be exclusively used to time light or exogenous melatonin treatment, as this could result in the mistiming of these treatments relative to the DLMO, thereby potentially worsening circadian misalignment.

A significant delay in the timing of endogenous circadian rhythms has been associated with delayed sleep phase disorder (DSPD). More recently, other mechanisms have also been proposed to account for this disorder. To further explore the etiology of DSPD, the present study compared nocturnal melatonin profiles of 26 DSPD patients (18 males, 8 females; age, 21.73 ± 4.98 years) and 17 normally timed good sleepers (10 males, 7 females; age, 23.82 ± 5.23 years) in a time-free, dim-light (

Chronic heavy alcohol use is known to cause gut leakiness and alcoholic liver disease (ALD), but only 30% of heavy drinkers develop increased intestinal permeability and ALD. The hypothesis of this study was that disruption of circadian rhythms is a potential risk factor in actively drinking alcoholics for gut leakiness and endotoxemia. We studied 20 subjects with alcohol use disorder (AD) and 17 healthy controls (HC, 6 day workers, 11 night workers). Subjects wore a wrist actiwatch for 7 days and underwent a 24-h dim light phase assessment and urine collection for intestinal permeability. The AD group had significantly less total sleep time and increased fragmentation of sleep ( P < 0.05). AD also had significantly lower plasma melatonin levels compared with the HC [mean area under the curve (AUC) 322.78 ± 228.21 vs. 568.75 ± 304.26 pg/ml, P = 0.03]. In the AD group, AUC of melatonin was inversely correlated with small bowel and colonic intestinal permeability (lactulose-to-mannitol ratio, r = −0.39, P = 0.03; urinary sucralose, r = −0.47, P = 0.01). Cosinor analysis of lipopolysaccharide-binding protein (marker of endotoxemia) and lipopolysaccharide every 4 h for 24 h in HC and AD subjects had a midline estimating statistic of rhythm of 5,026.15 ± 409.56 vs. 6,818.02 ± 628.78 ng/ml ( P < 0.01) and 0.09 ± 0.03 vs. 0.15 ± 0.19 EU/ml ( P < 0.05), respectively. We found plasma melatonin was significantly lower in the AD group, and lower melatonin levels correlated with increased intestinal permeability and a marker of endotoxemia. Our study suggests the suppression of melatonin in AD may promote gut leakiness and endotoxemia.

Little is known about the light exposure in full-time office workers, who spend much of their workdays indoors. We examined the 24-hour light exposure patterns of 14 full-time office workers during a week in summer, and assessed their dim light melatonin onset (DLMO, a marker of circadian timing) at the end of the working week. Six workers repeated the study in winter. Season had little impact on the workers' schedules, as the timing of sleep, commute, and work did not vary by more than 30 minutes in the summer and winter. In both seasons, workers received significantly more morning light on workdays than weekends, due to earlier wake times and the morning commute. Evening light in the two hours before bedtime was consistently dim. The timing of the DLMO did not vary between season, and by the end of the working week, the workers slept at a normal circadian phase.

We sought to establish the feasibility and preliminary effects of home-wearable light therapy for postpartum depression, and its effects on circadian measures. Eight women within 6 months postpartum were prescribed 60 min of daily morning light therapy for 5 weeks. The device was well tolerated. Significant improvements were observed in self-report and clinician-rated depression symptoms, with little change in objective circadian measures. Home-wearable light therapy is feasible for postpartum women and may be a promising treatment for postpartum depression. Clinicaltrials.gov Identifier: NCT02769858

We studied 28 adolescents/young adults with autism spectrum disorders (ASD) and 13 age/sex matched individuals of typical development (TD). Structured sleep histories, validated questionnaires, actigraphy (four weeks), and salivary cortisol and melatonin (four days each) were collected. Compared to those with TD, adolescents/young adults with ASD had longer sleep latencies and more difficulty going to bed and falling asleep. Morning cortisol, evening cortisol, and the morning-evening difference in cortisol did not differ by diagnosis (ASD vs. TD). Dim light melatonin onsets (DLMOs) averaged across participants were not different for the ASD and TD participants. Average participant scores indicated aspects of poor sleep hygiene in both groups. Insomnia in ASD is multifactorial and not solely related to physiological factors.

This review summarizes recent developments relevant to the treatment of circadian rhythm sleep-wake disorders. The clinical practice guidelines for the treatment of intrinsic circadian rhythm sleep-wake disorders is described, followed by recent treatment studies for delayed sleep-wake phase disorder, non-24 hour sleep-wake disorder, irregular sleep-wake disorder and shift work. New methods to estimate circadian phase, including home saliva collection to estimate the dim light melatonin onset, circadian questionnaires and general rules to guide light and exogenous melatonin treatments are described. New developments in light treatment are detailed, including light flashes during sleep and wearable light devices. Substances such as caffeine and alcohol, and devices such as electronic tablets are also considered for their potential to shift circadian timing. Finally, an update on melatonin supplements in the US is discussed, along with the controversy surrounding the use of melatonin supplements in patients with prediabetes or diabetes.

The efficacy of bright light and/or melatonin treatment for Delayed Sleep Wake Phase Disorder (DSWPD) is contingent upon an accurate clinical assessment of the circadian phase. However, the process of determining this circadian phase can be costly and is not yet readily available in the clinical setting. The present study investigated whether more cost-effective and convenient estimates of the circadian phase, such as self-reported sleep timing, can be used to predict the circadian phase and guide the timing of light and/or melatonin treatment (i.e. dim-light melatonin onset, core body temperature minimum and melatonin secretion mid-point) in a sample of individuals with DSWPD.Twenty-four individuals (male = 17; mean age = 21.96, SD = 5.11) with DSWPD were selected on the basis of ICSD-3 criteria from a community-based sample. The first 24-hours of a longer 80-hour constant laboratory ultradian routine were used to determine core body temperature minimum (cBTSignificant moderate to strong positive correlations were observed between self-reported sleep timing variables and DLMO, cBTThese findings suggest that self-reported sleep timing may be useful clinically to predict a therapeutically relevant circadian phase in DSWPD.

Our objectives were to investigate the period lengths (i.e., taus) of the endogenous core body temperature rhythm and melatonin rhythm in delayed sleep-wake phase disorder patients (DSWPD) and non-24-h sleep-wake rhythm disorder patients (N24SWD) compared with normally entrained individuals. Circadian rhythms were measured during an 80-h ultradian modified constant routine consisting of 80 ultrashort 1-h “days” in which participants had 20-min sleep opportunities alternating with 40 min of enforced wakefulness. We recruited a community-based sample of 26 DSWPD patients who met diagnostic criteria (17 males, 9 females; age, 21.85 ± 4.97 years) and 18 healthy controls (10 males, 8 females; age, 23.72 ± 5.10 years). Additionally, 4 full-sighted patients (3 males, 1 female; age, 25.75 ± 4.99 years) were diagnosed with N24SWD and included as a discrete study group. Ingestible core temperature capsules were used to record minute temperatures that were averaged to obtain 80 hourly data points. Salivary melatonin concentration was assessed every half-hour to determine time of dim light melatonin onset at the beginning and end of the 80-h protocol. DSWPD patients had significantly longer melatonin rhythm taus (24 h 34 min ± 17 min) than controls (24 h 22 min ± 15 min, p = 0.03, d = 0.70). These results were further supported by longer temperature rhythm taus in DSWPD patients (24 h 34 min ± 26 min) relative to controls (24 h 13 min ± 15 min, p = 0.01, d = 0.80). N24SWD patients had even longer melatonin (25 h ± 19 min) and temperature (24 h 52 min ± 17 min) taus than both DSWPD ( p = 0.007, p = 0.06) and control participants ( p < 0.001, p = 0.02, respectively). Between 12% and 19% of the variance in DSWPD patients’ sleep timing could be explained by longer taus. This indicates that longer taus of circadian rhythms may contribute to the DSWPD patients’ persistent tendency to delay, their frequent failure to respond to treatment, and their relapse following treatment. Additionally, other factors can contribute to misalignments in DSWPD and N24SWD disorders.

Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20–30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption.

Central circadian timing influences mental and physical health. Research in nocturnal rodents has demonstrated that when alcohol is consumed, it reaches the central hypothalamic circadian pacemaker (suprachiasmatic nuclei) and can directly alter circadian phase shifts to light. In two separate studies, we examined, for the first time, the effects of a single dose of alcohol on circadian phase advances and phase delays to light in humans. Two 23-day within-subjects placebo-controlled counterbalanced design studies were conducted. Both studies consisted of 6 days of fixed baseline sleep to stabilize circadian timing, a 2-day laboratory session, a 6-day break, and a repeat of 6 days of fixed sleep and a 2-day laboratory session. In the phase advance study ( n = 10 light drinkers, 24–45 yr), the laboratory sessions consisted of a baseline dim light phase assessment, sleep episode, alcohol (0.6 g/kg) or placebo, 2-h morning bright light pulse, and final phase assessment. In the phase-delay study ( n = 14 light drinkers, 22–44 yr), the laboratory sessions consisted of a baseline phase assessment, alcohol (0.8 g/kg) or placebo, 2-h late night bright light pulse, sleep episode, and final phase assessment. In both studies, alcohol either increased or decreased the observed phase shifts to light (interaction P ≥ 0.46), but the effect of alcohol vs. placebo on phase shifts to light was always on average smaller than 30 min. Thus, no meaningful effects of a single dose of alcohol vs. placebo on circadian phase shifts to light in humans were observed.

Summary Short sleep/dark durations are common in modern society. We investigated if exposure to additional evening ambient light, often associated with later bedtimes and short sleep, reduces circadian phase advances to morning bright light. Twelve healthy subjects participated in two conditions that differed in the distribution of sleep before exposure to morning bright light. Subjects had a consolidated 9-h night time sleep opportunity, or a 3-h daytime nap followed by a 6-h night time sleep opportunity, each before morning bright light. Eight of the 12 subjects obtained similar amounts of sleep in both conditions, and yet still showed significant reductions in phase advances with 6-h nights (1.7 versus 0.7 h, P

The dim light melatonin onset (DLMO) is the most reliable circadian phase marker in humans, but the cost of assaying samples is relatively high. Therefore, the authors examined differences between DLMOs calculated from hourly versus half-hourly sampling and differences between DLMOs calculated with two recommended thresholds (a fixed threshold of 3 pg/mL and a variable “3k” threshold equal to the mean plus two standard deviations of the first three low daytime points). The authors calculated these DLMOs from salivary dim light melatonin profiles collected from 122 individuals (64 women) at baseline. DLMOs derived from hourly sampling occurred on average only 6–8 min earlier than the DLMOs derived from half-hourly saliva sampling, and they were highly correlated with each other (r ≥ 0.89, p < .001). However, in up to 19% of cases the DLMO derived from hourly sampling was >30 min from the DLMO derived from half-hourly sampling. The 3 pg/mL threshold produced significantly less variable DLMOs than the 3k threshold. However, the 3k threshold was significantly lower than the 3 pg/mL threshold (p < .001). The DLMOs calculated with the 3k method were significantly earlier (by 22–24 min) than the DLMOs calculated with the 3 pg/mL threshold, regardless of sampling rate. These results suggest that in large research studies and clinical settings, the more affordable and practical option of hourly sampling is adequate for a reasonable estimate of circadian phase. Although the 3 pg/mL fixed threshold is less variable than the 3k threshold, it produces estimates of the DLMO that are further from the initial rise of melatonin.

Inflammatory bowel disease (IBD) is a waxing and waning disease characterized by diarrhea, abdominal pain and weight loss. Recently, there has been an increased interest in the roles that sleep, circadian rhythms and melatonin could have as regulators of inflammation in the Gl tract. Advances in our understanding of the molecular machinery of the circadian clock, and the discovery of clock genes in the GI tract are opening up new avenues of research for a role of sleep in IBD. Altering circadian rhythm significantly worsens the development of colitis in animal models, and preliminary human studies have shown that patients with IBD are at increased risk for altered sleep patterns. Further research is needed to clarify the role of disturbances in IBD.

Partial sleep deprivation is increasingly common in modern society. This study examined for the first time if partial sleep deprivation alters circadian phase shifts to bright light in humans. Thirteen young healthy subjects participated in a repeated-measures counterbalanced design with 2 conditions. Each condition had baseline sleep, a dim-light circadian phase assessment, a 3-day phase-advancing protocol with morning bright light, then another phase assessment. In one condition (no sleep deprivation), subjects had an 8-h sleep opportunity per night during the advancing protocol. In the other condition (partial sleep deprivation), subjects were kept awake for 4 h in near darkness (

Exogenous melatonin is increasingly used for its phase shifting and soporific effects. We generated a three pulse phase response curve (PRC) to exogenous melatonin (3 mg) by administering it to free-running subjects. Young healthy subjects (n = 27) participated in two 5 day laboratory sessions, each preceded by at least a week of habitual, but fixed sleep. Each 5 day laboratory session started and ended with a phase assessment to measure the circadian rhythm of endogenous melatonin in dim light using 30 min saliva samples. In between were three days in an ultradian dim light (< 150 lux)‐dark cycle (LD 2.5 : 1.5) during which each subject took one pill per day at the same clock time (3 mg melatonin or placebo, double blind, counterbalanced). Each individual’s phase shift to exogenous melatonin was corrected by subtracting their phase shift to placebo (a free-run). The resulting PRC has a phase advance portion peaking about 5 h before the dim light melatonin onset, in the afternoon. The phase delay portion peaks about 11 h after the dim light melatonin onset, shortly after the usual time of morning awakening. A dead zone of minimal phase shifts occurred around the first half of habitual sleep. The fitted maximum advance and delay shifts were 1.8 h and 1.3 h, respectively. This new PRC will aid in determining the optimal time to administer exogenous melatonin to achieve desired phase shifts and demonstrates that using exogenous melatonin as a sleep aid at night has minimal phase shifting effects.

Circadian (body clock) timing has a profound influence on mental health, physical health, and health behaviors. This review focuses on how light, melatonin, and other melatonin receptor agonist drugs can be used to shift circadian timing in patients with misaligned circadian rhythms. A brief overview of the human circadian system is provided, followed by a discussion of patient characteristics and safety considerations that can influence the treatment of choice. The important features of light treatment, light avoidance, exogenous melatonin, and other melatonin receptor agonists are reviewed, along with some of the practical aspects of light and melatonin treatment.

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.

to the editor: We thank Dr. Kawada for his interest in our recent article ([5][1]) and for raising several important issues related to the analysis of actigraphy in alcoholics. First, as noted in his letter we did use the default setting of 40 for sleep/wake sensitivity. We did this to permit

Summary The dim light melatonin onset (DLMO) assists with the diagnosis and treatment of circadian rhythm sleep disorders. Home DLMOs are attractive for cost savings and convenience, but can be confounded by home lighting and sample timing errors. We developed a home saliva collection kit with objective measures of light exposure and sample timing. We report on our first test of the kit in a clinical population. Thirty-two participants with delayed sleep phase disorder (DSPD; 17 women, aged 18–52 years) participated in two back-to-back home and laboratory phase assessments. Most participants (66%) received at least one 30-s epoch of light >50 lux during the home phase assessments, but for only 1.5% of the time. Most participants (56%) collected every saliva sample within 5 min of the scheduled time. Eighty-three per cent of home DLMOs were not affected by light or sampling errors. The home DLMOs occurred, on average, 10.2 min before the laboratory DLMOs, and were correlated highly with the laboratory DLMOs (r = 0.93, P

Study objectives There is a need for the accurate assessment of circadian phase outside of the clinic/laboratory, particularly with the gold standard dim light melatonin onset (DLMO). We tested a novel kit designed to assist in saliva sampling at home for later determination of the DLMO. The home kit includes objective measures of compliance to the requirements for dim light and half-hourly saliva sampling. Design Participants were randomized to one of two 10-day protocols. Each protocol consisted of two back-to-back home and laboratory phase assessments in counterbalanced order, separated by a 5-day break. Setting Laboratory or participants' homes. Participants Thirty-five healthy adults, age 21-62 y. Interventions N/A. Measurements and results Most participants received at least one 30-sec epoch of light > 50 lux during the home phase assessments (average light intensity 4.5 lux), but on average for 50 lux or sampling errors. There was no significant difference between the home and laboratory DLMOs (P > 0.05); on average the home DLMOs occurred 9.6 min before the laboratory DLMOs. The home DLMOs were highly correlated with the laboratory DLMOs (r = 0.91, P Conclusions Participants were reasonably compliant to the home phase assessment procedures. The good agreement between the home and laboratory dim light melatonin onsets (DLMOs) demonstrates that including objective measures of light exposure and sample timing during home saliva sampling can lead to accurate home DLMOs. Clinical trial registration Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252, NCT01487252.

Both light and melatonin can be used to phase shift the human circadian clock, but the phase-advancing effect of the combination has not been extensively investigated.The objective of the study was to determine whether phase advances induced by morning intermittent bright light and a gradually advancing sleep schedule could be increased with afternoon melatonin.Healthy adults (25 males, 19 females, between the ages of 19 and 45 yr) participated in the study.There were 3 d of a gradually advancing sleep/dark period (wake time 1 h earlier each morning), bright light on awakening [four 30-min bright-light pulses (approximately 5000 lux) alternating with 30 min room light60 lux] and afternoon melatonin, either 0.5 or 3.0 mg melatonin timed to induce maximal phase advances, or matching placebo. The dim light melatonin onset was measured before and after the treatment to determine the phase advance.There were significantly larger phase advances with 0.5 mg (2.5 h, n = 16) and 3.0 mg melatonin (2.6 h, n = 13), compared with placebo (1.7 h, n = 15), but there was no difference between the two melatonin doses. Subjects did not experience jet lag-type symptoms during the 3-d treatmentAfternoon melatonin, morning intermittent bright light, and a gradually advancing sleep schedule advanced circadian rhythms almost 1 h/d and thus produced very little circadian misalignment. This treatment could be used in any situation in which people need to phase advance their circadian clock, such as before eastward jet travel or for delayed sleep phase syndrome.

The time at which the dim light melatonin onset (DLMO) occurs can be used to ensure the correct timing of light and/or melatonin administration in order to produce desired circadian phase shifts. Sometimes however, measuring the DLMO is not feasible. Here we determined if the DLMO was best estimated from fixed sleep times (based on habitual sleep times) or free (ad libitum) sleep times. Young healthy sleepers on fixed (n = 60) or free (n = 60) sleep schedules slept at home for 6 days. Sleep times were recorded with sleep logs verified with wrist actigraphy. Half-hourly saliva samples were then collected during a dim light phase assessment and were later assayed to determine the DLMO. We found that the DLMO was more highly correlated with sleep times in the free sleepers than in the fixed sleepers (DLMO versus wake time, r = 0.70 and r = 0.44, both P < 0.05). The regression equation between wake time and the DLMO in the free sleepers predicted the DLMO in an independent sample of free sleepers (n = 23) to within 1.5 h of the actual DLMO in 96% of cases. These results indicate that the DLMO can be readily estimated in people whose sleep times are minimally affected by work, class and family commitments. Further work is necessary to determine if the DLMO can be accurately estimated in people with greater work and family responsibilities that affect their sleep times, perhaps by using weekend wake times, and if this method will apply to the elderly and patients with circadian rhythm disorders.

The aim of the study was to examine the adaptation of participants to a common night work schedule using urinary 6-sulphatoxymelatonin (aMT6s) concentration as the circadian phase marker. Fifteen adults (7 male, 8 female, age = 21.9 yr) spent nine consecutive nights in the laboratory, including: (i) adaptation sleep, (ii) baseline sleep, and (iii) seven simulated night shifts (23:00-07:00 h) followed by daytime sleep. During the baseline and daytime sleeps, participants collected urine samples which were subsequently assayed for aMT6s. The concentration of aMT6s in urine for the first three day sleeps was significantly lower than for the baseline sleep, but there was no difference in aMT6s concentrations between any of the last three day sleeps and the baseline sleep. The data indicate that people may adapt to a pattern of work that includes seven consecutive night shifts if they adhere to a fixed sleep schedule, if their exposure to morning sunlight is minimised, and if they are provided with an ideal sleep environment.

Small shifts in circadian timing occur frequently as a result of daylight saving time or later weekend sleep. These subtle shifts in circadian phase have been shown to influence subjective sleepiness, but it remains unclear if they can significantly affect performance. In a retrospective analysis we examined performance on the Psychomotor Vigilance Test before bedtime and after wake time in 11 healthy adults on fixed sleep schedules based on their habitual sleep times. The dim light melatonin onset, a marker of circadian timing, was measured on two occasions. An average 1.1 hour shift away from a proposed optimal circadian phase angle (6 hours between melatonin onset and midpoint of sleep) significantly slowed mean, median and fastest 10% reaction times before bedtime and after wake time (p

The endogenous melatonin onset in dim light (DLMO) is a marker of circadian phase that can be used to appropriately time the administration of bright light or exogenous melatonin in order to elicit a desired phase shift. Determining an individual's circadian phase can be costly and time-consuming. We examined the relationship between the DLMO and sleep times in 16 young healthy individuals who slept at their habitual times for a week. The DLMO occurred about 2 hours before bedtime and 14 hours after wake. Wake time and midpoint of sleep were significantly associated with the DLMO (r = 0.77, r = 0.68 respectively), but bedtime was not (r = 0.36). The possibility of predicting young healthy normally entrained people's DLMOs from their sleep times is discussed.

Supplemental melatonin has been used to treat sleep onset insomnia in children with autism spectrum disorders (ASD), although the mechanism of action is uncertain. We assessed endogenous and supplemental melatonin profiles in relation to sleep in nine children with ASD. In endogenous samples, maximal melatonin concentration (C(max)) and time to peak concentration (T(max)) were comparable to those previously published in the literature for typically developing children, and dim light melatonin onsets were captured in the majority of children. In treatment samples (supplemental melatonin), melatonin parameters were also comparable to those previously published for typically developing children. Our findings support that children with ASD and insomnia responsive to low dose melatonin treatment have relatively normal profiles of endogenous and supplemental melatonin.

The circadian clock establishes rhythms throughout the body with an approximately 24 hour period that affect expression of hundreds of genes. Epidemiological data reveal chronic circadian misalignment, common in our society, significantly increases the risk for a myriad of diseases, including cardiovascular disease, diabetes, cancer, infertility and gastrointestinal disease. Disruption of intestinal barrier function, also known as gut leakiness, is especially important in alcoholic liver disease (ALD). Several studies have shown that alcohol causes ALD in only a 20-30% subset of alcoholics. Thus, a better understanding is needed of why only a subset of alcoholics develops ALD. Compelling evidence shows that increased gut leakiness to microbial products and especially LPS play a critical role in the pathogenesis of ALD. Clock and other circadian clock genes have been shown to regulate lipid transport, motility and other gut functions. We hypothesized that one possible mechanism for alcohol-induced intestinal hyperpermeability is through disruption of central or peripheral (intestinal) circadian regulation. In support of this hypothesis, our recent data shows that disruption of circadian rhythms makes the gut more susceptible to injury. Our in vitro data show that alcohol stimulates increased Clock and Per2 circadian clock proteins and that siRNA knockdown of these proteins prevents alcohol-induced permeability. We also show that intestinal Cyp2e1-mediated oxidative stress is required for alcohol-induced upregulation of Clock and Per2 and intestinal hyperpermeability. Our mouse model of chronic alcohol feeding shows that circadian disruption through genetics (in Clock(▵19) mice) or environmental disruption by weekly 12h phase shifting results in gut leakiness alone and exacerbates alcohol-induced gut leakiness and liver pathology. Our data in human alcoholics show they exhibit abnormal melatonin profiles characteristic of circadian disruption. Taken together our data support circadian mechanisms for alcohol-induced gut leakiness that could provide new therapeutic targets for ALD.

Laboratory studies suggest that evening light before bedtime can suppress melatonin. Here, we measured the range of evening light intensity people can generate with their household lights, and for the first time determined if varying home light before usual bedtime can shift circadian phase. This was a 3-week study with two counterbalanced conditions separated by a 5-day break. In a dim week, eight healthy subjects minimized their home light exposure from 4 h before habitual bedtime until a self-selected bedtime. In a bright week, the subjects maximized their home lighting for the same time. The dim light melatonin onset (DLMO) was assessed after each week. On average subjects maximized their lights to approximately 65 lux and minimized their lights to approximately 3 lux. Wrist actigraphy indicated that subjects went to bed slightly later when lights were maximized (average 14 min later, P = 0.05), but wake time did not change. Every subject had a later DLMO after the week of maximum versus minimum light exposure (average 1:03 h later, P < 0.001). These results demonstrate that the light intensity people can generate at home in the few hours before habitual bedtime can alter circadian timing. People should reduce their evening light exposure to lessen circadian misalignment.

Patients with inflammatory bowel disease (IBD) complain of poor sleep [1,2], specifically of prolonged sleep latency, repeated awakenings, and poorer sleep quality than healthy controls, even in remission [1]. Possible contributors to this poor sleep include abdominal pain, diarrhea, bathroom trips, stress about future flare-ups, conditioned insomnia, altered immune function, and/or systemic inflammation [1,2]. Circadian disruption can also disturb sleep [3] and is linked to increased incidence of ulcers [4], colorectal cancer [5], and IBD [6]. We recently showed that chronic circadian disruption significantly exacerbates chemically induced colitis in mice, leading to greater weight loss, intestinal tissue injury, and colonic inflammation [7]. To date, circadian state has not been assessed in IBD patients. The gold standard measure of the circadian clock in humans is the melatonin rhythm [8]. This pilot study had two aims: (1) to determine if there was any circadian disruption in asymptomatic IBD patients (by examining the relationship between the timing of the melatonin rhythm and sleep) and (2) to determine if circulating melatonin levels were abnormally low, potentially contributing to the chronic inflammation and poor sleep in IBD. This is the first report of comprehensively measured melatonin rhythms in IBD patients. Four patients (two males, 22–39 years), three with Crohn’s disease and one with ulcerative colitis (clinical and histologically proven) participated. All were symptom free for at least 1 month prior. Patients were of normal weight and were not taking melatonin supplements, sleep aids, or nonsteriodal anti-inflammatory drugs (prescribed medications listed in Figure 1). All patients were nonsmokers and passed a drug screen, except Patient 2 who quit smoking at enrollment (at his own volition) and tested positive for marijuana. All patients had not worked night shifts or crossed time zones in the previous month. The patients wore wrist monitors (Actiwatch-L, Phillips) and followed their habitual sleep schedules for 8–9 days at home before their dim light salivary endogenous melatonin profiles were assessed as per standard procedures [9]. The protocol was approved by the Rush University Medical Center Institutional Review Board and was in accordance with the Declaration of Helsinki. Figure 1 Salivary melatonin profiles of four patients with asymptomatic inflammatory bowel disease. Each patient’s habitual sleep times are represented by a black rectangle. Patients stopped consuming alcohol and caffeine three days before the melatonin ... The wrist actigraphy data revealed that three patients had longer wake time after sleep onset than eight age and sex matched controls recruited online [10] (Table I). The patients’ sleep onset latency was significantly longer and sleep efficiency significantly lower than controls (Table I, both p < 0.05). These data are consistent with previous reports of poor sleep in patients with IBD. Table I The sleep parameters of the four IBD patients and eight matched control subjects during 7 days of baseline sleep. Three of the four patients had circadian rhythms in their melatonin secretion. The variability in the timing and amount of melatonin secreted was similar to a large sample of healthy controls [9]. The patients’ various medications did not abolish the melatonin rhythm in three patients. The lack of circadian rhythm in Patient 2’s melatonin secretion may have been due to his recent smoking and marijuana use. Nonetheless, the results indicate that the circadian rhythm in melatonin excretion can be abnormal in some patients with IBD and this should be studied in a larger cohort.

Multiple experimental approaches have been used to assess the free-running period, or “tau,” of humans. One approach has been to study circadian rhythms in free-running blind humans. For example, Sack et al. (1992) measured the plasma melatonin rhythm in 11 free-running blind people and reported an average tau of 24.55 h. In sighted humans, at least 3 different experimental paradigms have been used to derive tau. First, tau has been measured in people free-running in temporal isolation. In the classic bunker experiments, Wever (1979) reported an average tau of 25.00 h in 147 subjects. During spontaneous internal desynchronization in 52 of these subjects, tau from core body temperature recordings shortened to 24.86 h (Wever, 1992). Wever also noted shorter free-running periods in females, and longer free-running periods when subjects could alter light levels in association with their sleep, rather than sleeping in continuous ambient light. A background of constant bright light (3000–5000 lux) also lengthened tau (Wever, 1986, 1992). When subjects in the same isolation units were permitted to nap, tau was shorter in 3 subjects who napped (24.22 h) versus 4 subjects who rarely napped (24.73 h; Campbell et al., 1993). When groups of subjects lived in isolation units in dim light (

Publisher Summary Using bright light and melatonin to adjust to night work is indicated for people who want to work on a later schedule. This use of bright light and melatonin is specifically indicated for people who are working at least 2 consecutive weeks of night shifts, and particularly for workers engaged in high-risk work, such as nuclear power plant operators and health care workers. The circadian systems of night workers do not usually adjust to working at night and sleeping during the day. Instead, the circadian clock continues to promote sleep at night and wakefulness during the day. Thus, night shift work is associated with poor performance and excessive sleepiness during the night shift and poor daytime sleep at home. While hypnotics may pharmacologically induce daytime sleep, and stimulants (caffeine, modafinil) may reduce excessive sleepiness during the night shift, studies show that circadian-induced sleepiness during night shifts remains high. The health effects of the long-term use of these medications are unknown. Shift workers also have an increased risk for accidents, and for reproductive, cardiovascular, and gastrointestinal disorders and cancer. Many of these negative results are likely due in part to the chronic circadian misalignment that is characteristic of night work.

Publisher Summary Using bright light and melatonin to reduce jet lag is generally applicable to phase shifting the circadian clock in patients with circadian rhythm sleep disorders or winter depression. Bright light and melatonin can be used to reduce jet lag after crossing at least two time zones, east or west. Rapid jet travel across multiple time zones produces a temporary misalignment between the timing of the central circadian clock and the desired sleep times in the new time zone. This circadian misalignment often leads to nighttime insomnia (early insomnia after flying east, late insomnia after flying west), daytime sleepiness, worsened mood, and gastrointestinal disturbances. Bright light and melatonin can be used to accelerate the shifting of the circadian clock such that the circadian misalignment is minimized and the severity and duration of jet lag are reduced.

Context: Phase response curves (PRCs) to melatonin exist, but none compare different doses of melatonin using the same protocol. Objective: The aim was to generate a PRC to 0.5 mg of oral melatonin and compare it to our previously published 3.0 mg PRC generated using the same protocol. Design and Setting: The study included two 5-d sessions in the laboratory, each preceded by 7–9 d of fixed sleep times. Each session started and ended with a phase assessment to measure the dim light melatonin onset (DLMO). In between were 3 d in an ultradian dim light (

The length of the endogenous period of the human circadian clock (tau) is slightly greater than 24 hours. There are individual differences in tau, which influence the phase angle of entrainment to the light/dark (LD) cycle, and in doing so contribute to morningness-eveningness. We have recently reported that tau measured in subjects living on an ultradian LD cycle averaged 24.2 hours, and is similar to tau measured using different experimental methods. Here we report racial differences in tau. Subjects lived on an ultradian LD cycle (1.5 hours sleep, 2.5 hours wake) for 3 days. Circadian phase assessments were conducted before and after the ultradian days to determine the change in circadian phase, which was attributed to tau. African American subjects had a significantly shorter tau than subjects of other races. We also tested for racial differences in our previous circadian phase advancing and phase delaying studies. In the phase advancing study, subjects underwent 4 days of a gradually advancing sleep schedule combined with a bright light pulse upon awakening each morning. In the phase delaying study, subjects underwent 4 days of a gradually delaying sleep schedule combined with evening light pulses before bedtime. African American subjects had larger phase advances and smaller phase delays, relative to Caucasian subjects. The racial differences in tau and circadian phase shifting have important implications for understanding normal phase differences between individuals, for developing solutions to the problems of jet lag and shift work, and for the diagnosis and treatment of circadian rhythm based sleep disorders such as advanced and delayed sleep phase disorder.