Extending weeknight sleep of delayed adolescents using weekend morning bright light and evening time management.

STUDY OBJECTIVES: Shift sleep onset earlier and extend school-night sleep duration of adolescents. METHODS: Forty-six adolescents (14.5-17.9 years; 24 females) with habitual short sleep (≤7 h) and late bedtimes (≥23:00) on school nights slept as usual for 2 weeks (baseline). Then, there were three weekends and two sets of five weekdays in between. Circadian phase (Dim Light Melatonin Onset, DLMO) was measured in the laboratory on the first and third weekend. On weekdays, the "Intervention" group gradually advanced school-night bedtime (1 h earlier than baseline during week 1; 2 h earlier than baseline during week 2). Individualized evening time management plans ("Sleep RouTeen") were developed to facilitate earlier bedtimes. On the second weekend, Intervention participants received bright light (~6000 lux; 2.5 h) on both mornings. A control group completed the first and third weekend but not the second. They slept as usual and had no evening time management plan. Weekday sleep onset time and duration were derived from actigraphy. RESULTS: Dim light melatonin onset (DLMO) advanced more in the Intervention (0.6 ±â€…0.8 h) compared to the Control (-0.1 ±â€…0.8 h) group. By week 2, the Intervention group fell asleep 1.5 ±â€…0.7 h earlier and sleep duration increased by 1.2 ±â€…0.7 h; sleep did not systematically change in the Control group. CONCLUSIONS: This multi-pronged circadian-based intervention effectively increased school-night sleep duration for adolescents reporting chronic sleep restriction. Adolescents with early circadian phases may only need a time management plan, whereas those with later phases probably need both time management and morning bright light. CLINICAL TRIALS: Teen School-Night Sleep Extension: An Intervention Targeting the Circadian System (#NCT04087603): https://clinicaltrials.gov/ct2/show/NCT04087603.

Circadian Phase Advances in Response to Weekend Morning Light in Adolescents With Short Sleep and Late Bedtimes on School Nights.

Many adolescents fall asleep too late to get enough sleep (8-10 h) on school nights. Morning bright light advances circadian rhythms and could help adolescents fall asleep earlier. Morning bright light treatment before school, however, is difficult to fit into their morning schedule; weekends are more feasible. We examined phase advances in response to morning light treatment delivered over one weekend. Thirty-seven adolescents (16 males; 14.7-18.0 years) who reported short school-night sleep (≤7 h) and late bedtimes (school-nights ≥23:00; weekend/non-school nights ≥24:00) slept as usual at home for ∼2 weeks ("baseline") and then kept a fixed sleep schedule (baseline school-night bed and wake-up times ±30 min) for ∼1 week before living in the lab for one weekend. Sleep behavior was measured with wrist actigraphy and sleep diary. On Saturday morning, we woke each participant 1 h after his/her midpoint of baseline weekend/non-school night sleep and 1 h earlier on Sunday. They remained in dim room light (∼20 lux) or received 1.5 or 2.5 h of intermittent morning bright light (∼6000 lux) on both mornings. The dim light melatonin onset (DLMO), a phase marker of the circadian timing system, was measured on Friday and Sunday evenings to compute the weekend circadian phase shift. The dim room light and 1.5-h bright light groups advanced the same amount (0.6 ± 0.4 and 0.6 ± 0.5 h). The 2.5-h bright light group advanced 1.0 ± 0.4 h, which was significantly more than the other groups. These data suggest that it is possible to phase advance the circadian clock of adolescents who have late bedtimes and short school-night sleep in one weekend using light that begins shortly after their sleep midpoint.

Late bedtimes prevent circadian phase advances to morning bright light in adolescents.

We examined phase shifts to bright morning light when sleep was restricted by delaying bedtimes. Adolescents (n = 6) had 10-h sleep/dark opportunities for 6 days. For the next 2 days, half were put to bed 4.5 h later and then allowed to sleep for 5.5 h (evening room light + sleep restriction). The others continued the 10-h sleep opportunities (sleep satiation). Then, sleep schedules were gradually shifted earlier and participants received bright light (90 min, ~6000 lux) after waking for 3 days. As expected, sleep satiation participants advanced (~2 h). Evening room light + sleep restriction participants did not shift or delayed by 2-4 h. Abbreviations: DLMO: dim light melatonin onset.

Free-running circadian period in adolescents and adults.

Sleep timing shifts later during adolescence (second decade). This trend reverses at ~20 years and continues to shift earlier into adulthood. The current analysis examined the hypothesis that a longer free-running circadian period during late adolescence (14-17 years) compared with adulthood (30-45 years) accounts for sleep timing differences. Sex and ancestry were also examined because previous reports find that women and those with African-American ancestry have shorter free-running periods. Circadian period was measured using an ultradian dark-light protocol (2 hr dark/sleep, 2 hr dim room light [~20 lux]/wake) over 3.4 days. Dim light melatonin onsets were measured before and after the ultradian protocol, from which the circadian period was derived. In contrast to our hypothesis, we found that free-running circadian period was similar in adolescents and adults. African-American adults had shorter free-running circadian periods compared with adults of other ancestries. This ancestry difference was not seen in the adolescent group. Finally, we observed a non-significant trend for shorter free-running circadian periods in females compared with males. These data suggest that age-related changes in circadian period after late adolescence do not account for sleep timing differences. These data provide further support for ancestry-related differences in period, particularly in adults. Whether the large difference in circadian period between African-American and other ancestries emerges later in development should be explored.

Circadian phase, circadian period and chronotype are reproducible over months.

The timing of the circadian clock, circadian period and chronotype varies among individuals. To date, not much is known about how these parameters vary over time in an individual. We performed an analysis of the following five common circadian clock and chronotype measures: 1) the dim light melatonin onset (DLMO, a measure of circadian phase), 2) phase angle of entrainment (the phase the circadian clock assumes within the 24-h day, measured here as the interval between DLMO and bedtime/dark onset), 3) free-running circadian period (tau) from an ultradian forced desynchrony protocol (tau influences circadian phase and phase angle of entrainment), 4) mid-sleep on work-free days (MSF from the Munich ChronoType Questionnaire; MCTQ) and 5) the score from the Morningness-Eveningness Questionnaire (MEQ). The first three are objective physiological measures, and the last two are measures of chronotype obtained from questionnaires. These data were collected from 18 individuals (10 men, eight women, ages 21-44 years) who participated in two studies with identical protocols for the first 10 days. We show how much these circadian rhythm and chronotype measures changed from the first to the second study. The time between the two studies ranged from 9 months to almost 3 years, depending on the individual. Since the full experiment required living in the laboratory for 14 days, participants were unemployed, had part-time jobs or were freelance workers with flexible hours. Thus, they did not have many constraints on their sleep schedules before the studies. The DLMO was measured on the first night in the lab, after free-sleeping at home and also after sleeping in the lab on fixed 8-h sleep schedules (loosely tailored to their sleep times before entering the laboratory) for four nights. Graphs with lines of unity (when the value from the first study is identical to the value from the second study) showed how much each variable changed from the first to the second study. The DLMO did not change more than 2 h from the first to the second study, except for two participants whose sleep schedules changed the most between studies, a change in sleep times of 3 h. Phase angle did not change by more than 2 h regardless of changes in the sleep schedule. Circadian period did not change more than 0.2 h, except for one participant. MSF did not change more than 1 h, except for two participants. MEQ did not change more than 10 points and the categories (e.g. M-type) did not change. Pearson's correlations for the DLMO between the first and second studies increased after participants slept in the lab on their individually timed fixed 8-h sleep schedules for four nights. A longer time between the two studies did not increase the difference between any of the variables from the first to the second study. This analysis shows that the circadian clock and chronotype measures were fairly reproducible, even after many months between the two studies.

Advancing the sleep/wake schedule impacts the sleep of African-Americans more than European-Americans.

There are differences in sleep duration between Blacks/African-Americans and Whites/European-Americans. Recently, we found differences between these ancestry groups in the circadian system, such as circadian period and the magnitude of phase shifts. Here we document the role of ancestry on sleep and cognitive performance before and after a 9-h advance in the sleep/wake schedule similar to flying east or having a large advance in sleep times due to shiftwork, both of which produce extreme circadian misalignment. Non-Hispanic African and European-Americans (N = 20 and 17 respectively, aged 21-43 years) were scheduled to four baseline days each with 8 h time in bed based on their habitual sleep schedule. This sleep/wake schedule was then advanced 9 h earlier for three days. Sleep was monitored using actigraphy. During the last two baseline/aligned days and the first two advanced/misaligned days, beginning 2 h after waking, cognitive performance was measured every 3 h using the Automated Neuropsychological Assessment Metrics (ANAM) test battery. Mixed model ANOVAs assessed the effects of ancestry (African-American or European-American) and condition (baseline/aligned or advanced/misaligned) on sleep and cognitive performance. There was decreased sleep and impaired performance in both ancestry groups during the advanced/misaligned days compared to the baseline/aligned days. In addition, African-Americans obtained less sleep than European-Americans, especially on the first two days of circadian misalignment. Cognitive performance did not differ between African-Americans and European-Americans during baseline days. During the two advanced/misaligned days, however, African-Americans tended to perform slightly worse compared to European-Americans, particularly at times corresponding to the end of the baseline sleep episodes. Advancing the sleep/wake schedule, creating extreme circadian misalignment, had a greater impact on the sleep of African-Americans than European-Americans. Ancestry differences in sleep appear to be exacerbated when the sleep/wake schedule is advanced, which may have implications for individuals undertaking shiftwork and transmeridian travel.

Sleep and cognitive performance of African-Americans and European-Americans before and during circadian misalignment produced by an abrupt 9-h delay in the sleep/wake schedule.

We conducted two studies of circadian misalignment in non-Hispanic African and European-Americans. In the first, the sleep/wake (light/dark) schedule was advanced 9 h, similar to flying east, and in the second these schedules were delayed 9 h, similar to flying west or sleeping during the day after night work. We confirmed that the free-running circadian period is shorter in African-Americans compared to European-Americans, and found differences in the magnitude and direction of circadian rhythm phase shifts which were related to the circadian period. The sleep and cognitive performance data from the first study (published in this journal) documented the impairment in both ancestry groups due to this extreme circadian misalignment. African-Americans slept less and performed slightly worse during advanced/misaligned days than European-Americans. The current analysis is of sleep and cognitive performance from the second study. Participants were 23 African-Americans and 22 European-Americans (aged 18-44 years). Following four baseline days (8 h time in bed, based on habitual sleep), the sleep/wake schedule was delayed by 9 h for three days. Sleep was monitored using actigraphy. During the last two baseline/aligned days and the first two delayed/misaligned days, beginning 2 h after waking, cognitive performance was assessed every 3 h using the Automated Neuropsychological Assessment Metrics (ANAM) battery. Mixed model ANOVAs assessed the effects of ancestry (African-American or European-American) and condition (baseline/aligned or delayed/misaligned) on sleep and performance. There was decreased sleep and impaired cognitive performance in both ancestry groups during the two delayed/misaligned days relative to baseline/aligned days. Sleep and cognitive performance did not differ between African-Americans and European-Americans during either baseline/aligned or delayed/misaligned days. While our previous work showed that an advance in the sleep/wake schedule impaired the sleep of African-Americans more than European-Americans, delaying the sleep/wake schedule impaired the sleep and cognitive performance of African-Americans and European-Americans equally.

Human Adolescent Phase Response Curves to Bright White Light.

Older adolescents are particularly vulnerable to circadian misalignment and sleep restriction, primarily due to early school start times. Light can shift the circadian system and could help attenuate circadian misalignment; however, a phase response curve (PRC) to determine the optimal time for receiving light and avoiding light is not available for adolescents. We constructed light PRCs for late pubertal to postpubertal adolescents aged 14 to 17 years. Participants completed 2 counterbalanced 5-day laboratory sessions after 8 or 9 days of scheduled sleep at home. Each session included phase assessments to measure the dim light melatonin onset (DLMO) before and after 3 days of free-running through an ultradian light-dark (wake-sleep) cycle (2 h dim [~20 lux] light, 2 h dark). In one session, intermittent bright white light (~5000 lux; four 20-min exposures) was alternated with 10 min of dim room light once per day for 3 consecutive days. The time of light varied among participants to cover the 24-h day. For each individual, the phase shift to bright light was corrected for the free-run derived from the other laboratory session with no bright light. One PRC showed phase shifts in response to light start time relative to the DLMO and another relative to home sleep. Phase delay shifts occurred around the hours corresponding to home bedtime. Phase advances occurred during the hours surrounding wake time and later in the afternoon. The transition from delays to advances occurred at the midpoint of home sleep. The adolescent PRCs presented here provide a valuable tool to time bright light in adolescents.

Sex and ancestry determine the free-running circadian period.

The endogenous, free-running circadian period (τ) determines the phase relationship that an organism assumes when entrained to the 24-h day. We found a shorter circadian period in African Americans compared to non-Hispanic European Americans (24.07 versus 24.33 h). We speculate that a short circadian period, closer to 24 h, was advantageous to humans living around the equator, but when humans migrated North out of Africa, where the photoperiod changes with seasons, natural selection favoured people with longer circadian periods. Recently, in evolutionary terms, immigrants came from Europe and Africa to America ('the New World'). The Europeans were descendents of people who had lived in Europe for thousands of years with changing photoperiods (and presumably longer periods), whereas Africans had ancestors who had always lived around the equator (with shorter periods). It may have been advantageous to have a longer circadian period while living in Europe early in the evolution of humans. In our modern world, however, it is better to have a shorter period, because it helps make our circadian rhythms earlier, which is adaptive in our early-bird-dominated society. European American women had a shorter circadian period than men (24.24 versus 24.41), but there was no sex difference in African Americans (24.07 for both men and women). We speculate that selection pressures in Europe made men develop a slightly longer period than women to help them track dawn which could be useful for hunters, but less important for women as gatherers.

Diagnosis and Treatment of Non-24-h Sleep-Wake Disorder in the Blind.

Non-24-h sleep-wake disorder (non-24) is a circadian rhythm disorder occurring in 55-70% of totally blind individuals (those lacking conscious light perception) in which the 24-h biological clock (central, hypothalamic, circadian pacemaker) is no longer synchronized, or entrained, to the 24-h day. Instead, the overt rhythms controlled by the biological clock gradually shift progressively earlier or later (free run) in accordance with the clock's near-24-h period, resulting in a recurrent pattern of daytime hypersomnolence and night-time insomnia. Orally administered melatonin and the melatonin agonist tasimelteon have been shown to entrain (synchronize) the circadian clock, resulting in improvements in night-time sleep and daytime alertness. We review the basic principles of circadian rhythms necessary to understand and treat non-24. The time of melatonin or tasimelteon administration must be considered carefully. For most individuals, those with circadian periods longer than 24 h, low-dose melatonin should be administered about 6 h before the desired bedtime, while in a minority, those with circadian periods shorter than 24 h (more commonly female individuals and African-Americans), melatonin should be administered at the desired wake time. Small doses (e.g., 0.5 mg of melatonin) that are not soporific would thus be preferable. Administration of melatonin or tasimelteon at bedtime will entrain individuals with non-24 but at an abnormally late time, resulting in continued problems with sleep and alertness. To date, tasimelteon has only been administered 1 h before the target bedtime in patients with non-24. Issues of cost, dose accuracy, and purity may figure into the decision of whether tasimelteon or melatonin is chosen to treat non-24. However, there are no head-to-head studies comparing efficacy, and studies to date show comparable rates of treatment success (entrainment).

Circadian rhythms of European and African-Americans after a large delay of sleep as in jet lag and night work.

Jet travel and night shift work produce large changes in when people sleep, work and eat; a challenge that was not encountered during most of our evolution. Successful adaptation would require the internal, master, circadian clock to make large phase shifts to reduce the circadian misalignment between circadian rhythms and the times for sleep, work and meals. We compared African-Americans and non-Hispanic European-Americans in how much their circadian clocks shifted after a 9 hour phase delay of the light/dark, sleep/wake and meal schedule, which has similarities to flying west or sleeping in the daytime after night shifts. We also measured their free-running circadian periods using a forced desynchrony protocol with a 5-h day. European-Americans had longer free-running periods and larger phase delays than African-Americans. Correlations (among all subjects, just African-Americans and just European-Americans) showed that longer circadian periods were associated with larger phase delays. Larger phase delays, facilitated by longer circadian periods, reduce jet lag after westward travel and make it easier to work night shifts and sleep during the daytime after night work. On the other hand, a shorter circadian period, which makes one more of a morning-type person, is better for most people given our early-bird dominated society.

Circadian rhythm phase shifts and endogenous free-running circadian period differ between African-Americans and European-Americans.

Successful adaptation to modern civilization requires the internal circadian clock to make large phase shifts in response to circumstances (e.g., jet travel and shift work) that were not encountered during most of our evolution. We found that the magnitude and direction of the circadian clock's phase shift after the light/dark and sleep/wake/meal schedule was phase-advanced (made earlier) by 9 hours differed in European-Americans compared to African-Americans. European-Americans had larger phase shifts, but were more likely to phase-delay after the 9-hour advance (to phase shift in the wrong direction). The magnitude and direction of the phase shift was related to the free-running circadian period, and European-Americans had a longer circadian period than African-Americans. Circadian period was related to the percent Sub-Saharan African and European ancestry from DNA samples. We speculate that a short circadian period was advantageous during our evolution in Africa and lengthened with northern migrations out of Africa. The differences in circadian rhythms remaining today are relevant for understanding and treating the modern circadian-rhythm-based disorders which are due to a misalignment between the internal circadian rhythms and the times for sleep, work, school and meals.

Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

OBJECTIVE: Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. METHODS: Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance. RESULTS: Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light. CONCLUSIONS: A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human circadian rhythms.

Melatonin in the afternoons of a gradually advancing sleep schedule enhances the circadian rhythm phase advance.

RATIONALE: We test methods to advance (shift earlier) circadian rhythms without producing misalignment between rhythms and sleep. We previously tested (1) a gradually advancing sleep/dark schedule plus morning bright light and afternoon/evening melatonin and (2) the same sleep schedule with only morning bright light. Now we report on the same sleep schedule with only afternoon/evening melatonin. OBJECTIVES: This study aims to examine phase advances, sleepiness, and performance in response to melatonin compared to placebo. METHODS: Twelve adults (five female individuals) aged 20-45 years (mean ± SD = 28.3 ± 7.3 years) completed this within-subjects placebo-controlled counterbalanced study. The participants slept on fixed 8-h sleep schedules for nine days. Then, sleep/dark was advanced by 1 h/day for three consecutive days of treatment. The participants took 3 mg of melatonin or placebo 11 h before baseline sleep midpoint (the optimal time to produce phase advances) on the first treatment day and 1 h earlier on each subsequent day. We measured the dim light melatonin onset before and after treatment. The participants rated subjective symptoms throughout the study. They completed the Psychomotor Vigilance Task and rated sleepiness from 1 h before pill ingestion until bedtime on each treatment day. RESULTS: Melatonin produced significantly larger advances (1.3 ± 0.7 h) compared to placebo (0.7 ± 0.7 h); however, in the hours between melatonin ingestion and bed, melatonin caused sleepiness and performance decrements. CONCLUSIONS: Adding afternoon/evening melatonin to the gradually advancing sleep schedule increased the phase advance, but given the side effects, like sleepiness, it is better to use morning bright light and perhaps a lower dose of melatonin.

Blacks (African Americans) have shorter free-running circadian periods than whites (Caucasian Americans).

The length of the free-running period (τ) affects how an animal re-entrains after phase shifts of the light-dark (LD) cycle. Those with shorter periods adapt faster to phase advances than those with longer periods, whereas those with longer periods adapt faster to phase delays than those with shorter periods. The free-running period of humans, measured in temporal isolation units and in forced desychrony protocols in which the day length is set beyond the range of entrainment, varies from about 23.5 to 26 h, depending on the individual and the experimental conditions (e.g., temporal isolation vs. forced desychrony). We studied 94 subjects free-running through an ultradian LD cycle, which was a forced desychrony with a day length of 4 h (2.5 h awake in dim light, ~35 lux, alternating with 1.5 h for sleep in darkness). Circadian phase assessments were conducted before (baseline) and after (final) three 24-h days of the ultradian LD cycle. During these assessments, saliva samples were collected every 30 min and subsequently analyzed for melatonin. The phase shift of the dim light melatonin onset (DLMO) from baseline to final phase assessment gave the free-running period. The mean ± SD period was 24.31 ± .23 h and ranged from 23.7 to 24.9 h. Black subjects had a significantly shorter free-running period than Whites (24.18 ± .23 h, N =20 vs. 24.37 ± .22 h, N = 55). We had a greater proportion of women than men in our Black sample, so to check the τ difference we compared the Black women to White women. Again, Black subjects had a significantly shorter free-running period (24.18 ± .23, N = 17 vs. 24.41 ± .23, N = 23). We did not find any sex differences in the free-running period. These findings give rise to several testable predictions: on average, Blacks should adapt quicker to eastward flights across time zones than Whites, whereas Whites should adjust quicker to westward flights than Blacks. Also, Blacks should have more difficulty adjusting to night-shift work and day sleep, which requires a phase delay. On the other hand, Whites should be more likely to have trouble adapting to the early work and school schedules imposed by society. More research is needed to confirm these results and predictions.

Human phase response curve to intermittent blue light using a commercially available device.

Light shifts the timing of the circadian clock according to a phase response curve (PRC). To date, all human light PRCs have been to long durations of bright white light. However, melanopsin, the primary photopigment for the circadian system, is most sensitive to short wavelength blue light. Therefore, to optimise light treatment it is important to generate a blue light PRC.We used a small, commercially available blue LED light box, screen size 11.2 × 6.6 cm at ∼50 cm, ∼200 µW cm(−2), ∼185 lux. Subjects participated in two 5 day laboratory sessions 1 week apart. Each session consisted of circadian phase assessments to obtain melatonin profiles before and after 3 days of free-running through an ultradian light­dark cycle (2.5 h wake in dim light, 1.5 h sleep in the dark), forced desynchrony protocol. During one session subjects received intermittent blue light (three 30 min pulses over 2 h) once a day for the 3 days of free-running, and in the other session (control) they remained in dim room light, counterbalanced. The time of blue light was varied among subjects to cover the entire 24 h day. For each individual, the phase shift to blue light was corrected for the free-run determined during the control session. The blue light PRC had a broad advance region starting in the morning and extending through the afternoon. The delay region started a few hours before bedtime and extended through the night. This is the first PRC to be constructed to blue light and to a stimulus that could be used in the real world.

Shift work: health, performance and safety problems, traditional countermeasures, and innovative management strategies to reduce circadian misalignment.

There are three mechanisms that may contribute to the health, performance, and safety problems associated with night-shift work: (1) circadian misalignment between the internal circadian clock and activities such as work, sleep, and eating, (2) chronic, partial sleep deprivation, and (3) melatonin suppression by light at night. The typical countermeasures, such as caffeine, naps, and melatonin (for its sleep-promoting effect), along with education about sleep and circadian rhythms, are the components of most fatigue risk-management plans. We contend that these, while better than nothing, are not enough because they do not address the underlying cause of the problems, which is circadian misalignment. We explain how to reset (phase-shift) the circadian clock to partially align with the night-work, day-sleep schedule, and thus reduce circadian misalignment while preserving sleep and functioning on days off. This involves controlling light and dark using outdoor light exposure, sunglasses, sleep in the dark, and a little bright light during night work. We present a diagram of a sleep-and-light schedule to reduce circadian misalignment in permanent night work, or a rotation between evenings and nights, and give practical advice on how to implement this type of plan.

Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg.

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 (<150 lux)/dark cycle (light:dark, 2.5:1.5). PARTICIPANTS: Healthy adults (16 men, 18 women) between the ages of 18 and 42 yr participated in the study. INTERVENTIONS: During the ultradian days of the laboratory sessions, each participant took one pill per day at the same clock time (0.5 mg melatonin or placebo, double blind, counterbalanced). MAIN OUTCOME MEASURE: Phase shifts to melatonin were derived by subtracting the phase shift to placebo. A PRC with time of pill administration relative to baseline DLMO and a PRC relative to midpoint of home sleep were generated. RESULTS: Maximum advances occurred when 0.5 mg melatonin was taken in the afternoon, 2-4 h before the DLMO, or 9-11 h before sleep midpoint. The time for maximum phase delays was not as distinct, but a fitted curve peaked soon after wake time. CONCLUSIONS: The optimal administration time for advances and delays is later for the lower dose of melatonin. When each dose of melatonin is given at its optimal time, both yield similarly sized advances and delays.

A compromise circadian phase position for permanent night work improves mood, fatigue, and performance.

STUDY OBJECTIVE: To assess night shift improvements in mood, fatigue, and performance when the misalignment between circadian rhythms and a night shift, day sleep schedule is reduced. DESIGN: Blocks of simulated night shifts alternated with days off. Experimental subjects had interventions to delay their circadian clocks to partially align with a night shift schedule. Control subjects had no interventions. Subjects were categorized according to the degree of circadian realignment independent of whether they were in the experimental or control groups. Twelve subjects were categorized as not re-entrained, 21 as partially re-entrained, and 6 as completely re-entrained. SETTING: Home sleep and laboratory night shifts. PARTICIPANTS: Young healthy adults. INTERVENTIONS: Experimental subjects had intermittent bright light pulses during night shifts, wore dark sunglasses outside, and had scheduled sleep episodes in darkness. MEASUREMENTS AND RESULTS: A computerized test battery was administered every 2 hours during day and night shifts. After about one week on the night shift schedule, which included a weekend off, the partially and completely re-entrained groups had markedly improved mood, fatigue, and performance compared to the group that was not re-entrained. The completely and partially re-entrained groups were similar to each other and had levels of mood, fatigue, and performance that were close to daytime levels. CONCLUSIONS: Partial re-entrainment to a permanent night shift schedule, which can be produced by feasible, inexpensive interventions, is associated with greatly reduced impairments during night shifts.