Morning Melatonin Has Limited Benefit as a Soporific For Daytime Sleep After Night Work

Exogenous melatonin administration in humans is known to exert both chronobiotic (phase shifting) and soporific effects. In a previous study in our lab, young, healthy, subjects worked five consecutive simulated night shifts (23:00 to 07:00 h) and slept during the day (08:30 to 15:30 h). Large phase delays of various magnitudes were produced by the study interventions, which included bright light exposure during the night shifts, as assessed by the dim light melatonin onset (DLMO) before (baseline) and after (final) the five night shifts. Subjects also ingested either 1.8 mg sustained‐release melatonin or placebo before daytime sleep. Although melatonin at this time should delay the circadian clock, this previous study found that it did not increase the magnitude of phase delays. To determine whether melatonin had a soporific effect, we controlled the various magnitudes of phase delay produced by the other study interventions. Melatonin (n=18) and placebo (n=18) groups were formed by matching a melatonin participant with a placebo participant that had a similar baseline and final DLMO (±1 h). Sleep log measurements of total sleep time (TST) and actigraphic measurements of sleep latency, TST, and three movement indices for the two groups were examined. Although melatonin was associated with small improvements in sleep quality and quantity, the differences were not statistically significant by analysis of variance. However, binomial analysis indicated that melatonin participants were more likely to sleep better than their placebo counterparts on some days with some measures. It was concluded that, the soporific effect of melatonin is small when administered prior to 7 h daytime sleep periods following night shift work.     

SLEEP LOGS OF YOUNG ADULTS WITH SELF-SELECTED SLEEP TIMES PREDICT THE DIM LIGHT MELATONIN ONSET

The purpose of this study was to determine whether a sleep log parameter could be used to estimate the circadian phase of normal, healthy, young adults who sleep at their normal times, and thus naturally have day-to-day variability in their times of sleep. Thus, we did not impose any restrictions on the sleep schedules of our subjects (n=26). For 14 d, they completed daily sleep logs that were verified with wrist activity monitors. On day 14, salivary melatonin was sampled every 30 min in dim light from 19:00 to 07:30h to determine the dim light melatonin onset (DLMO). Daily sleep parameters (onset, midpoint, and wake) were taken from sleep logs and averaged over the last 5, 7, and 14 d before determination of the DLMO. The mean DLMO was 22:48±01:30 h. Sleep onset and wake time averaged over the last 5 d were 01:44±01:41 and 08:44±01:26 h, respectively. The DLMO was significantly correlated with sleep onset, midpoint, and wake time, but was most strongly correlated with the mean midpoint of sleep from the last 5 d (r=0.89). The DLMO predicted using the mean midpoint of sleep from the last 5 d was within 1 h of the DLMO determined from salivary melatonin for 92% of the subjects; in no case did the difference exceed 1.5 h. The correlation between the DLMO and the score on the morningness-eveningness questionnaire was significant but comparatively weak (r=-0.48). We conclude that the circadian phase of normal, healthy day-active young adults can be accurately predicted using sleep times recorded on sleep logs (and verified by actigraphy), even when the sleep schedules are irregular.     

A compromise phase position for permanent night shift workers: circadian phase after two night shifts with scheduled sleep and light/dark exposure

Night shift work is associated with a myriad of health and safety risks. Phase-shifting the circadian clock such that it is more aligned with night work and day sleep is one way to attenuate these risks. However, workers will not be satisfied with complete adaptation to night work if it leaves them misaligned during days off. Therefore, the goal of this set of studies is to produce a compromise phase position in which individuals working night shifts delay their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off. This is the first in the set of studies describing the magnitude of circadian phase delays that occurs on progressively later days within a series of night shifts interspersed with days off. The series will be ended on various days in order to take a "snapshot" of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h for three weeks. Following this baseline period, there is a series of night shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min intermittent bright light pulses (approximately 3500 lux; approximately 1100 microW/cm2) once per hour during the night shifts, wear sunglasses that attenuate all visible wavelengths--especially short wavelengths ("blue-blockers")--while traveling home after the shifts, and sleep in the dark (08:30-15:30 h) after each night shift. Control subjects remain in typical dim room light (<50 lux) throughout the night shift, wear sunglasses that do not attenuate as much light, and sleep whenever they want after the night shifts. Circadian phase is determined from the circadian rhythm of melatonin collected during a dim light phase assessment at the beginning and end of each study. The sleepiest time of day, approximated by the body temperature minimum (Tmin), is estimated by adding 7 h to the dim light melatonin onset. In this first study, circadian phase was measured after two night shifts and day sleep periods. The Tmin of the experimental subjects (n=11) was 04:24+/-0.8 h (mean+/-SD) at baseline and 7:36+/-1.4 h after the night shifts. Thus, after two night shifts, the Tmin had not yet delayed into the daytime sleep period, which began at 08:30 h. The Tmin of the control subjects (n=12) was 04:00+/-1.2 h at baseline and drifted to 4:36+/-1.4 h after the night shifts. Thus, two night shifts with a practical pattern of intermittent bright light, the wearing of sunglasses on the way home from night shifts, and a regular sleep period early in the daytime, phase delayed the circadian clock toward the desired compromise phase position for permanent night shift workers. Additional night shifts with bright light pulses and daytime sleep in the dark are expected to displace the sleepiest time of day into the daytime sleep period, improving both nighttime alertness and daytime sleep but not precluding adequate sleep on days off.     

Bright-light exposure during daytime sleeping affects nocturnal melatonin secretion after simulated night work

The guidelines for night and shift workers recommend that after night work, they should sleep in a dark environment during the daytime. However, staying in a dark environment during the daytime reduces nocturnal melatonin secretion and delays its onset. Daytime bright-light exposure after night work is important for melatonin synthesis the subsequent night and for maintaining the circadian rhythms. However, it is not clear whether daytime sleeping after night work should be in a dim- or a bright-light environment for maintaining melatonin secretion. The aim of this study, therefore, was to evaluate the effect of bright-light exposure during daytime sleeping on nocturnal melatonin secretion after simulated night work. Twelve healthy male subjects, aged 24.8 ± 4.6 (mean ± SD), participated in 3-day sessions under two experimental conditions, bright light or dim light, in a random order. On the first day, the subjects entered the experimental room at 16:00 and saliva samples were collected every hour between 18:00 and 00:00 under dim-light conditions. Between 00:00 and 08:00, they participated in tasks that simulated night work. At 10:00 the next morning, they slept for 6 hours under either a bright-light condition (>3000 lx) or a dim-light condition (<50 lx). In the evening, saliva samples were collected as on the first day. The saliva samples were analyzed for melatonin concentration. Activity and sleep times were recorded by a wrist device worn throughout the experiment. In the statistical analysis, the time courses of melatonin concentration were compared between the two conditions by three-way repeated measurements ANOVA (light condition, day and time of day). The change in dim light melatonin onset (ΔDLMO) between the first and second days, and daytime and nocturnal sleep parameters after the simulated night work were compared between the light conditions using paired t-tests. The ANOVA results indicated a significant interaction (light condition and3 day) (p = .006). Post hoc tests indicated that in the dim-light condition, the melatonin concentration was significantly lower on the second day than on the first day (p = .046); however, in the bright-light condition, there was no significant difference in the melatonin concentration between the days (p = .560). There was a significant difference in ΔDLMO between the conditions (p = .015): DLMO after sleeping was advanced by 11.1 ± 17.4 min under bright-light conditions but delayed for 7.2 ± 13.6 min after sleeping under dim-light conditions. No significant differences were found in any sleep parameter. Our study demonstrated that daytime sleeping under bright-light conditions after night work could not reduce late evening melatonin secretion until midnight or delay the phase of melatonin secretion without decreasing the quality of the daytime sleeping. Thus, these results suggested that, to enhance melatonin secretion and to maintain their conventional sleep–wake cycle, after night work, shift workers should sleep during the daytime under bright-light conditions rather than dim-light conditions.     

A Compromise Phase Position for Permanent Night Shift Workers: Circadian Phase after Two Night Shifts with Scheduled Sleep and Light/Dark Exposure

Night shift work is associated with a myriad of health and safety risks. Phase‐shifting the circadian clock such that it is more aligned with night work and day sleep is one way to attenuate these risks. However, workers will not be satisfied with complete adaptation to night work if it leaves them misaligned during days off. Therefore, the goal of this set of studies is to produce a compromise phase position in which individuals working night shifts delay their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off. This is the first in the set of studies describing the magnitude of circadian phase delays that occurs on progressively later days within a series of night shifts interspersed with days off. The series will be ended on various days in order to take a “snapshot” of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h for three weeks. Following this baseline period, there is a series of night shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min intermittent bright light pulses (～3500 lux; ～1100 µW/cm²) once per hour during the night shifts, wear sunglasses that attenuate all visible wavelengths—especially short wavelengths (“blue‐blockers”)—while traveling home after the shifts, and sleep in the dark (08:30–15:30 h) after each night shift. Control subjects remain in typical dim room light (<50 lux) throughout the night shift, wear sunglasses that do not attenuate as much light, and sleep whenever they want after the night shifts. Circadian phase is determined from the circadian rhythm of melatonin collected during a dim light phase assessment at the beginning and end of each study. The sleepiest time of day, approximated by the body temperature minimum (T_min), is estimated by adding 7 h to the dim light melatonin onset. In this first study, circadian phase was measured after two night shifts and day sleep periods. The T_min of the experimental subjects (n=11) was 04:24±0.8 h (mean±SD) at baseline and 7:36±1.4 h after the night shifts. Thus, after two night shifts, the T_min had not yet delayed into the daytime sleep period, which began at 08:30 h. The T_min of the control subjects (n=12) was 04:00±1.2 h at baseline and drifted to 4:36±1.4 h after the night shifts. Thus, two night shifts with a practical pattern of intermittent bright light, the wearing of sunglasses on the way home from night shifts, and a regular sleep period early in the daytime, phase delayed the circadian clock toward the desired compromise phase position for permanent night shift workers. Additional night shifts with bright light pulses and daytime sleep in the dark are expected to displace the sleepiest time of day into the daytime sleep period, improving both nighttime alertness and daytime sleep but not precluding adequate sleep on days off.     

Circadian phase, sleepiness, and light exposure assessment in night workers with and without shift work disorder

Most night workers are unable to adjust their circadian rhythms to the atypical hours of sleep and wake. Between 10% and 30% of shiftworkers report symptoms of excessive sleepiness and/or insomnia consistent with a diagnosis of shift work disorder (SWD). Difficulties in attaining appropriate shifts in circadian phase, in response to night work, may explain why some individuals develop SWD. In the present study, it was hypothesized that disturbances of sleep and wakefulness in shiftworkers are related to the degree of mismatch between their endogenous circadian rhythms and the night-work schedule of sleep during the day and wake activities at night. Five asymptomatic night workers (ANWs) (3 females; [mean ± SD] age: 39.2 ± 12.5 yrs; mean yrs on shift = 9.3) and five night workers meeting diagnostic criteria (International Classification of Sleep Disorders [ICSD]-2) for SWD (3 females; age: 35.6 ± 8.6 yrs; mean years on shift = 8.4) participated. All participants were admitted to the sleep center at 16:00 h, where they stayed in a dim light (<10 lux) private room for the study period of 25 consecutive hours. Saliva samples for melatonin assessment were collected at 30-min intervals. Circadian phase was determined from circadian rhythms of salivary melatonin onset (dim light melatonin onset, DLMO) calculated for each individual melatonin profile. Objective sleepiness was assessed using the multiple sleep latency test (MSLT; 13 trials, 2-h intervals starting at 17:00 h). A Mann-Whitney U test was used for evaluation of differences between groups. The DLMO in ANW group was 04:42 ± 3.25 h, whereas in the SWD group it was 20:42 ± 2.21 h (z = 2.4; p 相似文献   

Combinations of bright light, scheduled dark, sunglasses, and melatonin to facilitate circadian entrainment to night shift work

Various combinations of interventions were used to phase-delay circadian rhythms to correct their misalignment with night work and day sleep. Young participants (median age = 22, n = 67) participated in 5 consecutive simulated night shifts (2300 to 0700) and then slept at home (0830 to 1530) in darkened bedrooms. Participants wore sunglasses with normal or dark lenses (transmission 15% or 2%) when outside during the day. Participants took placebo or melatonin (1.8 mg sustained release) before daytime sleep. During the night shifts, participants were exposed to a moving (delaying) pattern of intermittent bright light (approximately 5000 lux, 20 min on, 40 min off, 4-5 light pulses/night) or remained in dim light (approximately 150 lux). There were 6 intervention groups ranging from the least complex (normal sunglasses) to the most complex (dark sunglasses + bright light + melatonin). The dim light melatonin onset (DLMO) was assessed before and after the night shifts (baseline and final), and 7 h was added to estimate the temperature minimum (Tmin). Participants were categorized by their amount of reentrainment based on their final Tmin: not re-entrained (Tmin before the daytime dark/sleep period), partially re-entrained (Tmin during the first half of dark/sleep), or completely re-entrained (Tmin during the second half of dark/ sleep). The sample was split into earlier participants (baseline Tmin < or = 0700, sunlight during the commute home fell after the Tmin) and later participants (baseline Tmin > 0700). The later participants were completely re-entrained regardless of intervention group, whereas the degree of re-entrainment for the earlier participants depended on the interventions. With bright light during the night shift, almost all of the earlier participants achieved complete re-entrainment, and the phase delay shift was so large that darker sunglasses and melatonin could not increase its magnitude. With only room light during the night shift, darker sunglasses helped earlier participants phase-delay more than normal sunglasses, but melatonin did not increase the phase delay. The authors recommend the combination of intermittent bright light during the night shift, sunglasses (as dark as possible) during the commute home, and a regular, early daytime dark/sleep period if the goal is complete circadian adaptation to night-shift work.     

Shifts of the hormonal rhythms of melatonin and cortisol after a 4 h bright-light pulse in different diurnal types

If applied during corresponding times of the individual melatonin profiles, bright light shifts the circadian phase equally, irrespective of diurnal type. We examined 32 young men: 10 morning types, 11 evening types, and 11 with no predisposition; 16 with high and 16 with low melatonin production. Each completed a 40 h session that included two consecutive nights during which the participants remained, apart from two short breaks during the second day, in bed under an illumination level of 30 lux. A 4 h bright light pulse was applied just after the expected individual melatonin onset the first night to cause a delay of the hormonal profile the second night. Salivary levels of melatonin and cortisol were determined hourly. Melatonin was delayed by 108 min, and cortisol offset and onset by 47 and 110 min, respectively. The cortisol quiescent period (start and end of the quiescent period being defined by the decrease below and the increase above 60% of the average cortisol production between 18:00 and 09:00 h) was prolonged. In contrast to the other subgroups, the delay of melatonin synthesis was about 0.5 h shorter in morning types, and their cortisol quiescent period was shortened. The present study leads to the hypothesis that, despite individually scheduled light exposure, morning types are potentially disadvantaged due to elevated cortisol levels, if persisting, in career night workers.     

A week of simulated night work delays salivary melatonin onset

In most studies, the magnitude and rate of adaptation to various night work schedules is assessed using core body temperature as the marker of circadian phase. The aim of the current study was to assess adaptation to a simulated night work schedule using salivary dim light melatonin onset (DLMO) as an alternative circadian phase marker. It was hypothesised that the night work schedule would result in a phase delay, manifest in relatively later DLMO, but that this delay would be somewhat inhibited by exposure to natural light. Participants worked seven consecutive simulated 8-hour night shifts (23:00-07:00 h). By night 7, there was a mean cumulative phase delay of 5.5 hours, equivalent to an average delay of 0.8 hours per day. This indicates that partial circadian adaptation occurred in response to the simulated night work schedule. The radioimmunoassay used in the current study provides a sensitive assessment of melatonin concentration in saliva that can be used to determine DLMO, and thus provides an alternative phase marker to core body temperature, at least in laboratory studies.     

Timing Light Treatment for Eastward and Westward Travel Preparation

Jet lag degrades performance and operational readiness of recently deployed military personnel and other travelers. The objective of the studies reported here was to determine, using a narrow bandwidth light tower (500 nm), the optimum timing of light treatment to hasten adaptive circadian phase advance and delay. Three counterbalanced treatment order, repeated measures studies were conducted to compare melatonin suppression and phase shift across multiple light treatment timings. In Experiment 1, 14 normal healthy volunteers (8 men/6 women) aged 34.9±8.2 yrs (mean±SD) underwent light treatment at the following times: A) 06:00 to 07:00 h, B) 05:30 to 07:30 h, and C) 09:00 to 10:00 h (active control). In Experiment 2, 13 normal healthy subjects (7 men/6 women) aged 35.6±6.9 yrs, underwent light treatment at each of the following times: A) 06:00 to 07:00 h, B) 07:00 to 08:00 h, C) 08:00 to 09:00 h, and a no-light control session (D) from 07:00 to 08:00 h. In Experiment 3, 10 normal healthy subjects (6 men/4 women) aged 37.0±7.7 yrs underwent light treatment at the following times: A) 02:00 to 03:00 h, B) 02:30 to 03:30 h, and C) 03:00 to 04:00 h, with a no-light control (D) from 02:30 to 03:30 h. Dim light melatonin onset (DLMO) was established by two methods: when salivary melatonin levels exceeded a 1.0 pg/ml threshold, and when salivary melatonin levels exceeded three times the 0.9 pg/ml sensitivity of the radioimmunoasssy. Using the 1.0 pg/ml DLMO, significant phase advances were found in Experiment 1 for conditions A (p?<?.028) and B (p?<?0.004). Experiment 2 showed significant phase advances in conditions A (p?<?0.018) and B (p?<?0.003) but not C (p?<?0.23), relative to condition D. In Experiment 3, only condition B (p?<?0.035) provided a significant phase delay relative to condition D. Similar but generally smaller phase shifts were found with the 2.7 pg/ml DLMO method. This threshold was used to analyze phase shifts against circadian time of the start of light treatment for all three experiments. The best fit curve applied to these data (R²?=?0.94) provided a partial phase-response curve with maximum advance at approximately 9–11 h and maximum delay at approximately 5–6 h following DLMO. These data suggest largest phase advances will result when light treatment is started between 06:00 and 08:00 h, and greatest phase delays will result from light treatment started between 02:00 to 03:00 h in entrained subjects with a regular sleep wake cycle (23:00 to 07:00 h).     

Effects of Filtering Visual Short Wavelengths During Nocturnal Shiftwork on Sleep and Performance

Circadian phase resetting is sensitive to visual short wavelengths (450–480?nm). Selectively filtering this range of wavelengths may reduce circadian misalignment and sleep impairment during irregular light-dark schedules associated with shiftwork. We examined the effects of filtering short wavelengths (<480?nm) during night shifts on sleep and performance in nine nurses (five females and four males; mean age?±?SD: 31.3?±?4.6 yrs). Participants were randomized to receive filtered light (intervention) or standard indoor light (baseline) on night shifts. Nighttime sleep after two night shifts and daytime sleep in between two night shifts was assessed by polysomnography (PSG). In addition, salivary melatonin levels and alertness were assessed every 2?h on the first night shift of each study period and on the middle night of a run of three night shifts in each study period. Sleep and performance under baseline and intervention conditions were compared with daytime performance on the seventh day shift, and nighttime sleep following the seventh daytime shift (comparator). On the baseline night PSG, total sleep time (TST) (p?<?0.01) and sleep efficiency (p?=?0.01) were significantly decreased and intervening wake times (wake after sleep onset [WASO]) (p?=?0.04) were significantly increased in relation to the comparator night sleep. In contrast, under intervention, TST was increased by a mean of 40?min compared with baseline, WASO was reduced and sleep efficiency was increased to levels similar to the comparator night. Daytime sleep was significantly impaired under both baseline and intervention conditions. Salivary melatonin levels were significantly higher on the first (p?<?0.05) and middle (p?<?0.01) night shifts under intervention compared with baseline. Subjective sleepiness increased throughout the night under both conditions (p?<?0.01). However, reaction time and throughput on vigilance tests were similar to daytime performance under intervention but impaired under baseline on the first night shift. By the middle night shift, the difference in performance was no longer significant between day shift and either of the two night shift conditions, suggesting some adaptation to the night shift had occurred under baseline conditions. These results suggest that both daytime and nighttime sleep are adversely affected in rotating-shift workers and that filtering short wavelengths may be an approach to reduce sleep disruption and improve performance in rotating-shift workers. (Author correspondence: casper@lunenfeld.ca)     

Circadian Phase,Sleepiness, and Light Exposure Assessment in Night Workers With and Without Shift Work Disorder

Most night workers are unable to adjust their circadian rhythms to the atypical hours of sleep and wake. Between 10% and 30% of shiftworkers report symptoms of excessive sleepiness and/or insomnia consistent with a diagnosis of shift work disorder (SWD). Difficulties in attaining appropriate shifts in circadian phase, in response to night work, may explain why some individuals develop SWD. In the present study, it was hypothesized that disturbances of sleep and wakefulness in shiftworkers are related to the degree of mismatch between their endogenous circadian rhythms and the night-work schedule of sleep during the day and wake activities at night. Five asymptomatic night workers (ANWs) (3 females; [mean?±?SD] age: 39.2?±?12.5 yrs; mean yrs on shift?=?9.3) and five night workers meeting diagnostic criteria (International Classification of Sleep Disorders [ICSD]-2) for SWD (3 females; age: 35.6?±?8.6 yrs; mean years on shift?=?8.4) participated. All participants were admitted to the sleep center at 16:00?h, where they stayed in a dim light (<10 lux) private room for the study period of 25 consecutive hours. Saliva samples for melatonin assessment were collected at 30-min intervals. Circadian phase was determined from circadian rhythms of salivary melatonin onset (dim light melatonin onset, DLMO) calculated for each individual melatonin profile. Objective sleepiness was assessed using the multiple sleep latency test (MSLT; 13 trials, 2-h intervals starting at 17:00?h). A Mann-Whitney U test was used for evaluation of differences between groups. The DLMO in ANW group was 04:42?±?3.25?h, whereas in the SWD group it was 20:42?±?2.21?h (z = 2.4; p?<?.05). Sleep did not differ between groups, except the SWD group showed an earlier bedtime on off days from work relative to that in ANW group. The MSLT corresponding to night work time (01:00–09:00?h) was significantly shorter (3.6?±?.90?min: [M?±?SEM]) in the SWD group compared with that in ANW group (6.8?±?.93?min). DLMO was significantly correlated with insomnia severity (r = ?.68; p < .03), indicating that the workers with more severe insomnia symptoms had an earlier timing of DLMO. Finally, SWD subjects were exposed to more morning light (between 05:00 and 11:00?h) as than ANW ones (798 vs. 180 lux [M?±?SD], respectively z?=??1.7; p?<?.05). These data provide evidence of an internal physiological delay of the circadian pacemaker in asymptomatic night-shift workers. In contrast, individuals with SWD maintain a circadian phase position similar to day workers, leading to a mismatch/conflict between their endogenous rhythms and their sleep-wake schedule. (Author correspondence: vgumeny1@hfhs.org)     

Working under daylight intensity lamp: an occupational risk for developing circadian rhythm sleep disorder?

A 47-yr-old male was admitted to the Institute for Fatigue and Sleep Medicine complaining of severe fatigue and daytime sleepiness. His medical history included diagnosis of depression and chronic fatigue syndrome. Antidepressant drugs failed to improve his condition. He described a gradual evolvement of an irregular sleep-wake pattern within the past 20 yrs, causing marked distress and severe impairment of daily functioning. He had to change to a part-time position 7 yrs ago, because he was unable to maintain a regular full-time job schedule. A 10-day actigraphic record revealed an irregular sleep-wake pattern with extensive day-to-day variability in sleep onset time and sleep duration, and a 36 h sampling of both melatonin level and oral temperature (12 samples, once every 3 h) showed abnormal patterns, with the melatonin peak around noon and oral temperature peak around dawn. Thus, the patient was diagnosed as suffering from irregular sleep-wake pattern. Treatment with melatonin (5 mg, 2 h before bedtime) did not improve his condition. A further investigation of the patient's daily habits and environmental conditions revealed two important facts. First, his occupation required work under a daylight intensity lamp (professional diamond-grading equipment of more than 8000 lux), and second, since the patient tended to work late, the exposure to bright light occurred mostly at night. To recover his circadian rhythmicity and stabilize his sleep-wake pattern, we recommended combined treatment consisting of evening melatonin ingestion combined with morning (09:00 h) bright light therapy (0800 lux for 1 h) plus the avoidance of bright light in the evening. Another 10-day actigraphic study done only 1 wk after initiating the combined treatment protocol revealed stabilization of the sleep-wake pattern with advancement of sleep phase. In addition, the patient reported profound improvement in maintaining wakefulness during the day. This case study shows that chronic exposure to bright light at the wrong biological time, during the nighttime, may have serious effects on the circadian sleep-wake patterns and circadian time structure. Therefore, night bright light exposure must be considered to be a risk factor of previously unrecognized occupational diseases of altered circadian time structure manifested as irregularity of the 24 h sleep-wake cycle and melancholy.     

Sleepiness and sleep in a simulated "six hours on/six hours off" sea watch system

Ships are operated around the clock using rapidly rotating shift schedules called sea watch systems. Sea watch systems may cause fatigue, in the same way as other irregular working time arrangements. The present study investigated subjective sleepiness and sleep duration in connection with a 6 h on/6 h off duty system. The study was performed in a bridge simulator, very similar to those found on ships. Twelve officers divided into two groups participated in the study that lasted 66 h. Half of the subjects started with the 06:00-12:00 h watch and the other half with the 12:00-18:00 h watch. The subjects alternated between off-duty and on-duty for the remainder of the experimental period. Approximately halfway through the experiment, the 12:00-18:00 h watch was divided into two 3 h watches/off-duty periods. The effect of this was to reverse the on-duty/off-duty pattern between the two groups. This enabled all subjects to work the four possible watches (00:00-06:00 h, 06:00-12:00 h, 12:00-18:00 h, and 18:00-24:00 h) in an order that was essentially counterbalanced between groups. Ratings of sleepiness (Karolinska Sleepiness Scale; KSS) were obtained every 30 min during on-duty periods and if subjects were awake during off-duty periods. The subjectively rated duration of sleep was recorded after each off-duty period that preceded watch periods when KSS was rated. The results showed that the average level of sleepiness was significantly higher during the 00:00-06:00 h watch compared to the 12:00-18:00 h and 18:00-24:00 h watches, but not to the 06:00-12:00 h watch. Sleepiness also progressed significantly from the start toward the end of each watch, with the exception of the 06:00-12:00 h watch, when levels remained approximately stable. There were no differences between groups (i.e., the order between watches). Sleep duration during the 06:00-12:00 h off-duty period (3 h 29 min) was significantly longer than during the 12:00-18:00 h period (1 h 47 min) and the 18:00-24:00 h period (2 h 7 min). Sleep during the 00:00-06:00 h period (4 h 23 min) was longer than all sleep periods except the 06:00-12:00 h period. There were no differences between groups. In spite of sufficient opportunities for sleep, sleep was on the average around 1-1 h 30 min shorter than the 7-7 h 30 min that is considered “normal” during a 24 h period. This is probably a consequence of the difficulty to sleep during daytime due to the alerting effects of the circadian rhythm. Also, sleepiness during the night and early mornings reached high levels, which may be explained by a combination of working close to or during the circadian trough of alertness and the relatively short sleep periods obtained. An initial suppression of sleepiness was observed during all watches, except for the 06:00-12:00 h watch. This suppression may be explained by the “masking effect” exerted by the relative high levels of activity required when taking over the responsibility of the ship. Toward the end of watches, the levels of sleepiness progressively increased to relatively high levels, at least during the 00:00-06:00 h watch. Presumably, initially high levels of activity are replaced by routine and even boredom.     

Sleep logs of young adults with self-selected sleep times predict the dim light melatonin onset

The purpose of this study was to determine whether a sleep log parameter could be used to estimate the circadian phase of normal, healthy, young adults who sleep at their normal times, and thus naturally have day-to-day variability in their times of sleep. Thus, we did not impose any restrictions on the sleep schedules of our subjects (n = 26). For 14 d, they completed daily sleep logs that were verified with wrist activity monitors. On day 14, salivary melatonin was sampled every 30 min in dim light from 19:00 to 07:30 h to determine the dim light melatonin onset (DLMO). Daily sleep parameters (onset, midpoint, and wake) were taken from sleep logs and averaged over the last 5, 7, and 14 d before determination of the DLMO. The mean DLMO was 22:48 +/- 01:30 h. Sleep onset and wake time averaged over the last 5 d were 01:44 +/- 01:41 and 08:44 +/- 01:26 h, respectively. The DLMO was significantly correlated with sleep onset, midpoint, and wake time, but was most strongly correlated with the mean midpoint of sleep from the last 5 d (r = 0.89). The DLMO predicted using the mean midpoint of sleep from the last 5 d was within 1 h of the DLMO determined from salivary melatonin for 92% of the subjects; in no case did the difference exceed 1.5 h. The correlation between the DLMO and the score on the morningness-eveningness questionnaire was significant but comparatively weak (r = -0.48). We conclude that the circadian phase of normal, healthy day-active young adults can be accurately predicted using sleep times recorded on sleep logs (and verified by actigraphy), even when the sleep schedules are irregular.     

Increased REM sleep associated with melatonin deficiency after pinealectomy: a case study

The objectives of the investigation were to assess hypersomnia, which progressively appeared in a young patient after a pinealectomy, chemotherapy, and radiotherapy for a typical germinoma, as well as the potential benefit of melatonin administration in the absence of its endogenous secretion. 24 h ambulatory polysomnography and the Multiple Sleep Latency Test (MSLT) were performed; in addition, daily plasma melatonin, cortisol, growth hormone, prolactin, and rectal temperature profiles were determined before and during melatonin treatment (one 2 mg capsule given nightly at 21:00 h for 4 weeks). MSLT showed abnormal sleep latency and two REM sleep onsets. Nighttime total sleep duration was lengthened, mainly as a consequence of an increased REM sleep duration. These parameters were slightly modified by melatonin replacement. Plasma melatonin levels, which were constantly nil in the basal condition, were increased to supraphysiological values with melatonin treatment. The plasma cortisol profile showed nycthemeral variation within the normal range, and the growth hormone profile showed supplementary diurnal peaks. Melatonin treatment did not modify the secretion of either hormone. The plasma prolactin profile did not display a physiological nocturnal increase in the basal condition; however, it did during melatonin treatment, with the rise coinciding with the nocturnal peak of melatonin concentration. A 24 h temperature rhythm of normal amplitude was persistent, though the mean level was decreased and the rhythm was dampened during melatonin treatment. The role of radiotherapy on the studied parameters cannot be excluded; the findings of this case study suggest that the observed hypersomnia is not the result of melatonin deficiency alone. Overall, melatonin treatment was well tolerated, but the benefit on the sleep abnormality, especially on daytime REM sleep, was minor, requiring the re-introduction of modafinil treatment.     

A randomized controlled trial with bright light and melatonin for delayed sleep phase disorder: Effects on subjective and objective sleep

Delayed sleep phase disorder (DSPD) is assumed to be common amongst adolescents, with potentially severe consequences in terms of school attendance and daytime functioning. The most common treatment approaches for DSPD are based on the administration of bright light and/or exogenous melatonin with or without adjunct behavioural instructions. Much is generally known about the chronobiological effects of light and melatonin. However, placebo-controlled treatment studies for DSPD are scarce, in particular in adolescents and young adults, and no standardized guidelines exist regarding treatment. The aim of the present study was, therefore, to investigate the short- and long-term effects on sleep of a DSPD treatment protocol involving administration of timed bright light and melatonin alongside gradual advancement of rise time in adolescents and young adults with DSPD in a randomized controlled trial and an open label follow-up study. A total of 40 adolescents and young adults (age range 16–25 years) diagnosed with DSPD were recruited to participate in the study. The participants were randomized to receive treatment for two weeks in one of four treatment conditions: dim light and placebo capsules, bright light and placebo capsules, dim light and melatonin capsules or bright light and melatonin capsules. In a follow-up study, participants were re-randomized to either receive treatment with the combination of bright light and melatonin or no treatment in an open label trial for approximately three months. Light and capsules were administered alongside gradual advancement of rise times. The main end points were sleep as assessed by sleep diaries and actigraphy recordings and circadian phase as assessed by salivary dim light melatonin onset (DLMO). During the two-week intervention, the timing of sleep and DLMO was advanced in all treatment conditions as seen by about 1?h advance of bed time, 2?h advance of rise time and 2?h advance of DLMO in all four groups. Sleep duration was reduced with approximately 1?h. At three-month follow-up, only the treatment group had maintained an advanced sleep phase. Sleep duration had returned to baseline levels in both groups. In conclusion, gradual advancement of rise time produced a phase advance during the two-week intervention, irrespective of treatment condition. Termination of treatment caused relapse into delayed sleep times, whereas long-term treatment with bright light and melatonin (three months) allowed maintenance of the advanced sleep phase.     

Comparative study of the activity/rest rhythms in young and old ringdove (Streptopelia risoria): correlation with serum levels of melatonin and serotonin

Aging is characterized by changes in the circadian rhythms of melatonin, serotonin, and sleep/wakefulness, alterations that affect sleep quality. The authors studied the circadian rhythms of serotonin and melatonin in young and old ringdoves (Streptopelia risoria) (2-3 and 10-12 yrs old, respectively), animals that are characterized by being monophasic and active by day, like humans. The aim was to correlate the indole rhythms with the animals' activity/rest periods. The animals were kept under a 12:12 h light/dark cycle, fed ad libitum, and housed in separate cages equipped for activity recording. Activity pulses were recorded with one actometer per animal (two perpendicular infrared transmitters) and were logged every 15 min by a computer program (DAS 16) throughout the experiment. Melatonin was measured by radioimmunoassay and serotonin by ELISA at intervals of 3 h (from 09:00 to 18:00 h) and 1 h (from 21:00 to 06:00 h), respectively. The results showed a reduction in nocturnal vs. diurnal activity of 89% and 61% in the young and old animals, respectively, with 100% considered to be the diurnal activity of each group. The amplitude of a cosine function fit to the melatonin concentrations of the old animals was half that of the young birds. The acrophase and nadir were at 02:00 and 14:00 h in the young and 01:00 and 13:00 h in the old animals, respectively. The amplitude of the corresponding cosine function fit to the serotonin concentrations in the old birds was one-third that of the young animals. The acrophase and nadir were at 15:00 and 03:00 h in the young and 16:00 and 04:00 h in the old animals, respectively. For both melatonin and serotonin, the concentrations in the young animals were significantly higher than in the old at most of the measurement times. There was a clear negative correlation between the circadian rhythms of activity and the serum melatonin levels in both young and old animals. The equivalent correlation for serotonin was positive, and stronger in the case of the young animals. The results suggest a possible relationship between the observed decline in the amplitude of the old animals' melatonin and serotonin rhythms and the lower percentage reduction in their nocturnal relative to diurnal activity pulses compared to the young animals. In conclusion, the circadian rhythms of melatonin and serotonin undergo alterations with age that could be involved in the changes in age-associated sleep.     

Role of morning melatonin administration and attenuation of sunlight exposure in improving adaptation of night-shift workers

The authors studied whether melatonin administration improves adaptation of workers to nightshift and if its beneficial effect is enhanced by attenuation of morning sunlight exposure. Twelve nightshift nurses received three treatments: Placebo (Pla), Melatonin (Mel), and Melatonin with Sunglasses (Mel-S). Each treatment procedure was administered for 2 d of different 4d nightshifts in a repeated measures crossover design. In Pla, nurses were treated with placebo before daytime sleep and allowed exposure to morning sunlight. In Mel, 6 mg of melatonin was similarly administered before daytime sleep with morning sunlight permitted. In Mel-S, 6 mg of melatonin was given as in Mel, with sunglasses worn in the morning to attenuate sunlight exposure. Placebo or melatonin was administered during days 2 and 3 when the first and second daytime sleep occurred. Nocturnal alertness and performance plus daytime sleep and mood states were assessed during all three treatments. The sleep period and total sleep times were significantly increased by melatonin treatments; yet, nocturnal alertness was only marginally improved. There were no differences between Mel and Mel-S. Performance tests revealed no difference between Pla and melatonin treatments. Melatonin exerted modest benefit in improving the adaptation of workers to nightshift, and its effect was not enhanced by attenuation of morning sunlight exposure.     

Older poor-sleeping women display a smaller evening increase in melatonin secretion and lower values of melatonin and core body temperature than good sleepers

Melatonin concentration and core body temperature (CBT) follow endogenous circadian biological rhythms. In the evening, melatonin level increases and CBT decreases. These changes are involved in the regulation of the sleep-wake cycle. Therefore, the authors hypothesized that age-related changes in these rhythms affect sleep quality in older people. In a cross-sectional study design, 11 older poor-sleeping women (aged 62-72 yrs) and 9 older good-sleeping women (60-82 yrs) were compared with 10 younger good-sleeping women (23-28 yrs). The older groups were matched by age and body mass index. Sleep quality was assessed by the Pittsburgh Sleep Quality Index questionnaire. As an indicator of CBT, oral temperature was measured at 1-h intervals from 17:00 to 24:00?h. At the same time points, saliva samples were collected for determining melatonin levels by enzyme-linked immunosorbent assay (ELISA). The dim light melatonin onset (DLMO), characterizing the onset of melatonin production, was calculated. Evening changes in melatonin and CBT levels were tested by the Friedman test. Group comparisons were performed with independent samples tests. Predictors of sleep-onset latency (SOL) were assessed by regression analysis. Results show that the mean CBT decreased in the evening from 17:00 to 24:00?h in both young women (from 36.57°C to 36.25°C, p < .001) and older women (from 36.58°C to 35.88°C, p < .001), being lowest in the older poor sleepers (p < .05). During the same time period, mean melatonin levels increased in young women (from 16.2 to 54.1 pg/mL, p < .001) and older women (from 10.0 to 23.5 pg/mL, p < .001), being lowest among the older poor sleepers (from 20:00 to 24:00?h, p < .05 vs. young women). Older poor sleepers also showed a smaller increase in melatonin level from 17:00 to 24:00?h than older good sleepers (mean?±?SD: 7.0?±?9.63 pg/mL vs. 15.6?±?24.1 pg/mL, p = .013). Accordingly, the DLMO occurred at similar times in young (20:10?h) and older (19:57?h) good-sleeping women, but was delayed ～50?min in older poor-sleeping women (20:47?h). Older poor sleepers showed a shorter phase angle between DLMO and sleep onset, but a longer phase angle between CBT peak and sleep onset than young good sleepers, whereas older good sleepers had intermediate phase angles (insignificant). Regression analysis showed that the DLMO was a significant predictor of SOL in the older women (R(2)?=?0.64, p < .001), but not in the younger women. This indicates that melatonin production started later in those older women who needed more time to fall asleep. In conclusion, changes in melatonin level and CBT were intact in older poor sleepers in that evening melatonin increased and CBT decreased. However, poor sleepers showed a weaker evening increase in melatonin level, and their DLMO was delayed compared with good sleepers, suggesting that it is not primarily the absolute level of endogenous melatonin, but rather the timing of the circadian rhythm in evening melatonin secretion that might be related to disturbances in the sleep-wake cycle in older people.