Overnight urinary melatonin levels in women with and without HIV: An observational cohort study.

INTRODUCTION: Despite significant improvements in longevity and quality of life associated with antiretroviral therapy, individuals with HIV still suffer from a higher burden of sleep and circadian disruption and inflammatory-based diseases than individuals without HIV. While melatonin is a hormone that has a role in sleep and circadian regulation and has anti-inflammatory properties, the overnight concentration of the urinary melatonin metabolite has not yet been reported in people with HIV. METHODS: The aim of this study was to compare the overnight urinary melatonin metabolite levels in women aged 35-70 years with HIV (n = 151) to a well-matched comparison group of women without HIV (n = 147). All women wore a wrist actigraphy monitor and completed daily diaries documenting sleep timing and use of medications and drugs or alcohol for 10 days. Participants collected their overnight urine near the end of the monitoring period. RESULTS: Melatonin levels did not differ between women with or without HIV, but more than 40% of women had low levels of melatonin. Higher body mass index predicted lower levels of melatonin, and lower levels of melatonin were associated with lower sleep efficiency as assessed with wrist actigraphy. CONCLUSION: These data lay the foundation for exploration of the longitudinal consequences of endogenous melatonin levels for inflammatory-based diseases in aging women with and without HIV. Future studies should consider the use of supplemental melatonin to improve sleep in women with lower levels of melatonin.

A 4-week morning light treatment with stable sleep timing for individuals with fibromyalgia: a randomized controlled trial.

OBJECTIVES: Fibromyalgia is characterized by chronic widespread pain, mood, and sleep disturbance. Pharmacological treatments have modest efficacy and are associated with negative side effects, and alternative approaches are needed. Morning bright light treatment may assist in the management of fibromyalgia as it can reduce depressive symptoms, improve sleep, and advance circadian timing. METHODS: Sixty people with fibromyalgia (58 women, mean age 41.8 ± 13.3 years) were enrolled in a study comparing 4 weeks of a 1-hour daily morning bright light treatment (active treatment) to a morning dim light treatment (comparison treatment). Both light treatments included behavioral procedures to stabilize sleep timing. The morning bright light treatment was expected to produce larger improvements in pain and function than the dim light treatment and larger improvements in potential mediators (mood, sleep, and circadian timing). RESULTS: Both the bright and dim light treatment groups achieved significant but similar levels of improvement in pain intensity, pain interference, physical function, depressive symptoms, and sleep disturbance. Overall, the sample on average displayed a clinically meaningful improvement in the Fibromyalgia Impact Questionnaire-Revised score (mean reduction of 11.2 points), comparable to that reported following physical exercise treatments. Minimal side effects were observed. CONCLUSIONS: Findings indicate that the effects of a morning bright light treatment did not exceed those of a comparison dim light treatment; yet the changes on average in both conditions revealed clinically meaningful improvements. Future research is warranted to identify what elements of this trial may have contributed to the observed effects.

A matter of time: A systematic scoping review on a potential role of the circadian system in binge eating behavior.

Background: Emerging research suggests that food intake timing, eating behavior and food preference are associated with aspects of the circadian system function but the role that the circadian system may play in binge eating (BE) behavior in humans remains unclear. Objective: To systematically evaluate the evidence for circadian system involvement in BE behavior. Methods: Systematic searches of PubMed, EMBASE, and Scopus were performed for reports published from inception until May 2020 (PROSPERO Registration CRD42020186325). Searches were conducted by combining Medical Subject Headings related to the circadian system, BE behavior, and/or interventions. Observational and interventional studies in humans with BE behavior published in peer-review journals in the English language were included. Studies were assessed using quality and risk of bias tools (AXIS, ROB 2.0, or ROBINS). Results: The search produced 660 articles, 51 of which were included in this review. Of these articles, 46 were observational studies and 5 were interventional trials. Evidence from these studies suggests that individuals with BE behavior tend to have more food intake, more binge cravings, and more BE episodes later in the day. Hormonal and day/night locomotor activity rhythm disturbances may be associated with BE behavior. Furthermore, late diurnal preference ("eveningness") was associated with BE behavior and chronobiological interventions that shift the circadian clock earlier (e.g., morning bright light therapy) were found to possibly decrease BE behavior. Substantive clinical overlap exists between BE and night eating behavior. However, there is a significant knowledge gap regarding their potential relationship with the circadian system. Limitations include the lack of studies that use best-established techniques to assess the chronobiology of BE behavior, heterogeneity of participants, diagnostic criteria, and study design, which preclude a meta-analytic approach. Conclusion: Current evidence, although limited, suggests that the circadian system may play a role in the etiology of BE behavior. Further mechanistic studies are needed to fully characterize a potential role of the circadian system in BE behavior. A chronobiological approach to studying BE behavior may lead to identification of its neurobiological components and development of novel therapeutic interventions. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020186325], identifier [CRD42020186325].

Morning light treatment for traumatic stress: The role of amygdala reactivity study protocol.

BACKGROUND: Exposure to trauma can result in various mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although psychotherapies and pharmacotherapies exist for the treatment of these disorders, many individuals fail to receive treatment and among those who do, many remain symptomatic. Therefore, it is critical to continue developing new interventions for traumatic stress that target underlying mechanisms of pathology and offer a safe and acceptable alternative to current treatments. Morning light treatment has good potential as a novel non-invasive, low risk treatment for traumatic stress. Evidence suggests that morning light may improve traumatic stress by reducing reactivity in the amygdala, a brain region implicated in the pathophysiology of PTSD and anatomically linked to circadian photoreceptors in the eye. METHODS: In this study, we aim to establish a significant dose-response relationship between duration of morning light treatment and reduction in amygdala reactivity among individuals with traumatic stress symptoms (NCT# 04117347). Using a transdiagnostic approach, sixty-six individuals with a history of a DSM-5 criterion A trauma and traumatic stress symptoms will be recruited to participate in a 5-week study. Participants will be randomized across three treatment arms based on morning light treatment duration: 15-minutes, 30-minutes, or 60-minutes of light treatment per day for four weeks. To evaluate amygdala activity, participants will undergo fMRI at pre-treatment, mid-treatment, and post-treatment. Participants will also complete clinical assessments and self-report measures of PTSD, depression, and anxiety at pre-treatment, mid-treatment, and post-treatment. DISCUSSION: Morning light therapy may be an acceptable, feasible, and effective treatment for individuals suffering from traumatic stress. Identifying mechanistically relevant targets, and the doses needed to impact them, are critical steps in developing this new treatment approach for the sequelae of traumatic stress.

Morning light therapy in adults with Tourette's disorder.

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 2 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 a significant advance 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.

Workshop report. Circadian rhythm sleep-wake disorders: gaps and opportunities.

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.

Examining Insomnia During Intensive Treatment for Veterans with Posttraumatic Stress Disorder: Does it Improve and Does it Predict Treatment Outcomes?

Previous research has demonstrated that sleep disturbances show little improvement with evidence-based psychotherapy for posttraumatic stress disorder (PTSD); however, sleep improvements are associated with PTSD treatment outcomes. The goal of the current study was to evaluate changes in self-reported insomnia symptoms and the association between insomnia symptoms and treatment outcome during a 3-week intensive treatment program (ITP) for veterans with PTSD that integrated cognitive processing therapy (CPT), mindfulness, yoga, and other ancillary services. As part of standard clinical procedures, veterans (N = 165) completed self-report assessments of insomnia symptoms at pre- and posttreatment as well as self-report assessments of PTSD and depression symptoms approximately every other day during treatment. Most veterans reported at least moderate difficulties with insomnia at both pretreatment (83.0%-95.1%) and posttreatment (69.1-71.3%). Statistically significant reductions in self-reported insomnia severity occurred from pretreatment to posttreatment; however, the effect size was small, d = 0.33. Longitudinal mixed-effects models showed a significant interactive effect of Changes in Insomnia × Time in predicting PTSD and depression symptoms, indicating that patients with more improvements in insomnia had more positive treatment outcomes. These findings suggest that many veterans continued to struggle with sleep disruption after a 3-week ITP, and successful efforts to improve sleep could lead to better PTSD treatment outcomes. Further research is needed to establish how adjunctive sleep interventions can be used to maximize both sleep and PTSD outcomes.

Plasma DHA Is Related to Sleep Timing and Duration in a Cohort of Mexican Adolescents.

BACKGROUND: Delayed sleep timing and short sleep duration represent a significant public health burden in adolescents. Whether intake of nutrients affects the pineal gland, where sleep/wake cycles are regulated, remains unclear. OBJECTIVES: In a cross-sectional analysis, we investigated whether plasma concentrations of DHA and arachidonic acid (AA), long-chain fatty acids that can be obtained through diet, were related to sleep timing and duration in adolescents. METHODS: The study population included 405 Mexico City adolescents (mean age ± SD = 14.2 ± 2.1 y; 48% males) who took part in a 2015-2016 follow-up visit as a part of an ongoing cohort study. Fatty acid concentrations were measured in plasma using GLC, as a percentage of total fatty acids. Sleep midpoint and duration were assessed with 7-d wrist actigraphy. We categorized DHA and AA plasma concentrations into quartiles (Q1-Q4; Q4 = highest fatty acids). We conducted cross-sectional linear regression analysis with sleep characteristics as separate outcomes and quartiles of DHA and AA as exposures, adjusting for sex, age, and BMI z-scores. RESULTS: Mean ± SD plasma DHA (as percentage of total fatty acids) was 1.2 ± 0.4%, whereas mean ± SD plasma AA was 6.2 ± 1.5%. In adjusted analysis, higher plasma DHA was linearly associated with longer sleep duration on the weekends; to illustrate, those in Q4 compared with Q1 had 32 min longer duration (95% CI: 7, 57; P trend = 0.005). Higher DHA was also associated with earlier sleep timing during weekdays and weekends, although in a nonlinear fashion. The largest difference was a 0.75-h (45-min) later sleep midpoint in Q2 compared with Q4 (95% CI: 0.36, 1.14). CONCLUSIONS: Plasma DHA was associated with earlier sleep timing and longer weekend sleep duration in Mexican adolescents. Whether DHA supplementation improves sleep in adolescent populations deserves consideration in randomized trials.

A placebo-controlled pilot study of a wearable morning bright light treatment for probable PTSD.

BACKGROUND: Evidence-based treatments for post-traumatic stress disorder (PTSD) have poor uptake and remission rates, suggesting that alternative treatments are needed. Morning bright light may be an effective treatment for PTSD given its established effects on mood and sleep, however, there are no published trials. METHODS: We conducted a placebo-controlled pilot trial of a wearable light device, the Re-timer®, for individuals with probable PTSD. Individuals were randomly assigned to the active Re-timer® (n = 9) or a placebo Re-timer® dimmed with neutral density filters (n = 6). Participants self-administered the treatment at home 1 hr each morning over 4 weeks. PTSD and depression symptoms were assessed at pre- and post-treatment. RESULTS: The Re-timer® was well tolerated and the perceived benefit was high, though treatment adherence was only moderate. Those in the active group were more likely to achieve a minimal clinically important change in PTSD and depression symptoms and had larger symptom reductions than those in the placebo group CONCLUSIONS: A wearable morning light treatment was acceptable and feasible for patients with probable PTSD. This study provides initial proof-of-concept that light treatment can improve PTSD. A larger trial is warranted to establish treatment efficacy. NCT#: 03513848.

An Open Trial of Morning Bright Light Treatment Among US Military Veterans with Chronic Low Back Pain: A Pilot Study.

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 < 0.05). Phase advances in circadian timing were associated with reductions in pain interference (r = 0.55, P < 0.05). CONCLUSIONS: Morning bright light treatment is a feasible and acceptable treatment for US veterans with chronic low back pain. Those who undergo morning bright light treatment may show improvements in pain, pain sensitivity, and sleep. Advances in circadian timing may be one mechanism by which morning bright light reduces pain. Morning bright light treatment should be further explored as an innovative treatment for chronic pain conditions.

An open-label pilot study of a home wearable light therapy device for postpartum depression.

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.

Morning Versus Evening Bright Light Treatment at Home to Improve Function and Pain Sensitivity for Women with Fibromyalgia: A Pilot Study.

Objective: To test the feasibility, acceptability, and effects of a home-based morning versus evening bright light treatment on function and pain sensitivity in women with fibromyalgia. Design: A single blind randomized study with two treatment arms: 6 days of a 1 hour morning light treatment or 6 days of a 1 hour evening light treatment. Function, pain sensitivity, and circadian timing were assessed before and after treatment. Setting: Participants slept at home, except for two nights in Sleep Center. Participants: Ten women meeting the American College of Rheumatology's diagnostic criteria for fibromyalgia, including normal blood test results. Methods: Self-reported function was assessed with the Fibromyalgia Impact Questionnaire (FIQ). Pain sensitivity was assessed using a heat stimulus that gave measures of threshold and tolerance. Circadian timing was assessed with the dim light melatonin onset. Results: Both morning and evening light treatments led to improvements in function and pain sensitivity. However, only the morning light treatment led to a clinically meaningful improvement in function (>14% reduction from baseline FIQ) and morning light significantly increased pain threshold more than evening light ( P < 0.05). Phase advances in circadian timing were associated with an increase in pain tolerance (r = 0.67, P < 0.05). Conclusions: Bright light treatment appears to be a feasible and acceptable adjunctive treatment to women with fibromyalgia. Those who undergo morning light treatment may show improvements in function and pain sensitivity. Advances in circadian timing may be one mechanism by which morning light improves pain sensitivity. Findings can inform the design of a randomized controlled trial.

The etiology of delayed sleep phase disorder.

According to classification manuals for sleep disorders, nine disorders are directly related to biological clock timing misalignments. Of all, delayed sleep phase disorder (DSPD) is the most commonly diagnosed, predominantly affecting adolescents, young adults, and insomnia patients. It is a persistent inability to fall asleep at earlier, more desirable and socially conventional times, coupled with extreme difficulty awakening in the morning. Considerable evidence shows a delay in the circadian clock to be associated with DSPD. Therefore, treatments have mainly focused on advancing the biological clock and sleep timing through pharmacotherapy, phototherapy and behavioral therapies. The clinical evidence indicates that these treatments are efficacious, at least in the short term. However, follow up studies show frequent patient relapse, leading researchers to speculate that alternative etiologies may be contributing to sleep and circadian clock delays in DSPD. The aim of the present paper is to review and collate current literature related to DSPD etiology in order to outline gaps in current knowledge and suggest future research.

Effect of Light and Melatonin and Other Melatonin Receptor Agonists on Human Circadian Physiology.

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.

Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline.

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.

Nocturnal Melatonin Profiles in Patients with Delayed Sleep-Wake Phase Disorder and Control Sleepers.

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 (<10 lux) laboratory environment. A 30-h modified constant routine with alternating 20-min sleep opportunities and 40 min of enforced wakefulness was used to measure the endogenous melatonin circadian rhythm. Salivary melatonin was sampled half-hourly from 1820 h to 0020 h and then hourly from 0120 h to 1620 h. DSPD patients had significantly later timed melatonin profiles that were delayed by approximately 3 h compared to normal sleepers, and there were no notable differences in the relative duration of secretion between groups. However, melatonin secretion between dim-light melatonin onset (DLMO) and acrophase was less prominent in DSPD patients compared to good sleepers, who showed a more acute initial surge of melatonin following the DLMO. Although the regulatory role of melatonin is unknown, abnormal melatonin profiles have been linked to psychiatric and neurological disorders (e.g., major depression, obsessive compulsive disorder, Parkinson disease). These results therefore suggest that in addition to a delayed endogenous circadian rhythm, a diminished initial surge of melatonin secretion following DLMO may contribute to the etiology of DSPD.

Melatonin in children with autism spectrum disorders: endogenous and pharmacokinetic profiles in relation to sleep.

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 endogenous circadian temperature period length (tau) in delayed sleep phase disorder compared to good sleepers.

The currently assumed aetiology for delayed sleep phase disorder (DSPD) is a delay of the circadian system. Clinicians have sought to use bright light therapy, exogenous melatonin or chronotherapy to correct the disorder. However, these treatments have achieved unreliable outcomes for DSPD patients and, as such, one suggestion has been that the disorder may be caused by a longer than normal circadian rhythm period length (i.e. tau). The present study investigated this premise using a 78-h ultradian, ultra-short sleep-wake cycle. This constant bedrest routine was used to simulate a series of 1-h long 'days' by alternating 20-min sleep opportunities and 40 min of enforced wakefulness. Thirteen participants were recruited for the study including, six people diagnosed with DSPD according to the International Classification of Sleep Disorders-2 [mean age = 22.0, standard deviation (SD) = 3.3] and seven good sleepers (mean age = 23.1, SD = 3.9) with normal sleep timing. The DSPD participants' core temperature rhythm tau (mean = 24 h 54 min, SD = 23 min) was significantly longer (t = -2.33, P = 0.04, Cohen's d = 1.91) than the good sleepers' (mean 24 h 29 min, SD = 16 min). The temperature rhythm of the DSPD participants delayed more rapidly (i.e. >25 min day(-1) ) than the good sleepers'. These findings provide an explanation for the difficulty that DSPD patients have in phase advancing to a more conventional sleep time and their frequent relapse following treatment. The outcomes of this study support a vigorous and continued application of chronobiological and behavioural therapies to entrain DSPD patients to their desired earlier sleep times.

Advancing circadian rhythms before eastward flight: a strategy to prevent or reduce jet lag.

STUDY OBJECTIVES: To develop a practical pre-eastward flight treatment to advance circadian rhythms as much as possible but not misalign them with sleep. DESIGN: One group had their sleep schedule advanced by 1 hour per day and another by 2 hours per day. SETTING: Baseline at home, treatment in lab. PARTICIPANTS: Young healthy adults (11 men, 15 women) between the ages of 22 and 36 years. INTERVENTIONS: Three days of a gradually advancing sleep schedule (1 or 2 hours per day) plus intermittent morning bright light (one-half hour approximately 5000 lux, one-half hour of <60 lux) for 3.5 hours. MEASUREMENTS AND RESULTS: The dim light melatonin onset was assessed before and after the 3-day treatment. Subjects completed daily sleep logs and symptom questionnaires and wore wrist activity monitors. The dim light melatonin onset advanced more in the 2-hours-per-day group than in the 1-hour-per-day group (median phase advances of 1.9 and 1.4 hours), but the difference between the means (1.8 and 1.5 hours) was not statistically significant. By the third treatment day, circadian rhythms were misaligned relative to the sleep schedule, and subjects had difficulty falling asleep in the 2-hours-per-day group, but this was not the case in the 1-hour-per-day group. Nevertheless, the 2-hours-per-day group did slightly better on the symptom questionnaires. In general, sleep disturbance and other side effects were small. CONCLUSIONS: A gradually advancing sleep schedule with intermittent morning bright light can be used to advance circadian rhythms before eastward flight and, thus, theoretically, prevent or reduce subsequent jet lag. Given the morning light treatment used here, advancing the sleep schedule 2 hours per day is not better than advancing it 1 hour per day because it was too fast for the advance in circadian rhythms. A diagram is provided to help the traveler plan a preflight schedule.