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)     

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.     

School start time influences melatonin and cortisol levels in children and adolescents – a community-based study

School start time influences sleep parameters. Differences between circadian sleep parameters on weekends and weekdays have been associated with obesity, sleep, and psychiatric disorders. Moreover, circadian rhythm dysregulation affects the secretion of some hormones, such as melatonin and cortisol. In the current study, we investigate the effect of school start time on cortisol and melatonin levels in a community sample of Brazilian children and adolescents. This was a cross-sectional study of 454 students (mean age, 12.81 ± 2.56 years; 58.6% female). From this sample, 80 participants were randomly selected for saliva collection to measure melatonin and cortisol levels. Circadian sleep parameters were assessed by self-reported sleep and wake up schedules and the Morningness–Eveningness Questionnaire. The outcomes, salivary melatonin and cortisol levels, were measured in morning, afternoon and night saliva samples, and behavior problems were assessed using the Child Behavior Checklist (CBCL). The main results revealed that morning school start time decreased the secretion of melatonin. Morning melatonin levels were significantly positively correlated with the sleep midpoint on weekdays and on weekends. Afternoon melatonin levels were positively correlated with the sleep midpoint on weekends in the morning school students. Conversely, in the afternoon school students, night melatonin levels were negatively correlated with the sleep midpoint on weekdays. Cortisol secretion did not correlate with circadian sleep parameters in any of the school time groups. In conclusion, school start time influences melatonin secretion, which correlated with circadian sleep parameters. This correlation depends on the presence of psychiatric symptoms. Our findings emphasize the importance of drawing attention to the influence of school start time on the circadian rhythm of children and adolescents.     

Is there a 24-hour rhythm in alcohol craving and does it vary by sleep/circadian timing?

ABSTRACT

Increasing evidence implicates sleep/circadian factors in alcohol use; however, the role of such factors in alcohol craving has received scant attention. Prior research suggests a 24-hour rhythm in related processes (e.g., reward motivation), but more research directly investigating a rhythm in craving is needed. Moreover, prior evidence is ambiguous whether such a rhythm in alcohol craving may vary by sleep/circadian timing. To examine these possibilities, 36 late adolescents (18–22 years of age; 61% female) with regular alcohol use but without a current alcohol use disorder were recruited to complete smartphone reports of alcohol craving intensity six times a day for two weeks. During these two weeks, participants wore wrist actigraphs and completed two in-lab assessments (on Thursday and Sunday) of dim light melatonin onset (DLMO). Average actigraphically derived midpoint of sleep on weekends and average DLMO were used as indicators of sleep and circadian timing, respectively. Multilevel cosinor analysis revealed a 24-hour rhythm in alcohol craving. Findings across the sleep and circadian timing variables converged to suggest that sleep/circadian timing moderated the 24-hour rhythm in alcohol craving. Specifically, people with later sleep/circadian timing had later timing of peak alcohol craving. These findings add to the growing evidence of potential circadian influences on reward-related phenomena and suggest that greater consideration of sleep and circadian influences on alcohol craving may be useful for understanding alcohol use patterns and advancing related interventions.     

Dim Light Melatonin Onset in Alcohol-Dependent Men and Women Compared with Healthy Controls

Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean?±?SD age: 36.0?±?11.0 yrs of age, 10 women) who were 3–12 wks since their last drink (abstinence: 57.9?±?19.3 d) and 19 age- and sex-matched HCs (34.4?±?10.6 yrs, 5 women). Following a 23:00–06:00?h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00?h bedtime) during which salivary melatonin samples were collected every 30?min beginning at 19:30?h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02?±?00:41?h, than in HC, 20:44?±?00:21?h (t?=??2.4, p?=?.02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18?min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats. (Author correspondence: daconroy@med.umich.edu)     

Dim light melatonin onset in alcohol-dependent men and women compared with healthy controls

Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean?±?SD age: 36.0?±?11.0 yrs of age, 10 women) who were 3-12 wks since their last drink (abstinence: 57.9?±?19.3 d) and 19 age- and sex-matched HCs (34.4?±?10.6 yrs, 5 women). Following a 23:00-06:00?h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00?h bedtime) during which salivary melatonin samples were collected every 30?min beginning at 19:30?h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02?±?00:41?h, than in HC, 20:44?±?00:21?h (t?=?-2.4, p?=?.02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18?min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats.     

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   

The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes

Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100?mg?day^?1 of melatonin or placebo 30?min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase-shift delay of the melatonin circadian rhythm, with an acrophase at 05:00?h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep–wake cycle, improving sleep efficiency.     

Circadian Phase in Adults of Contrasting Ages

There is evidence that aging may impair phase‐shifting responses to light synchronizers, which could lead to disturbed or malsynchronized circadian rhythms. To explore this hypothesis, 62 elder participants (age, 58 to 84 years) and 25 young adults (age, 19 to 40 years) were studied, first with baseline 1‐wk wrist actigraphy at home and then by 72 h in‐laboratory study using an ultra‐short sleep‐wake cycle. Subjects were awake for 60 minutes in 50 lux followed by 30 minutes of darkness for sleep. Saliva samples were collected for melatonin, and urine samples were collected for aMT6s (a urinary metabolite of melatonin) and free cortisol every 90 minutes. Oral temperatures were also measured every 90 minutes. The timing of the circadian rhythms was not significantly more variable among the elders. The times of lights‐out and wake‐up at home and urinary free cortisol occurred earlier among elders, but the acrophases (cosinor analysis‐derived peak time) of the circadian rhythm of salivary melatonin, urinary aMT6s, and oral temperature were not significantly phase‐advanced among elders. The estimated duration of melatonin secretion was 9.9 h among elders and 8.4 h among young adults (p<0.025), though the estimated half‐life of blood melatonin was shorter among elders (p<0.025), and young adults had higher saliva melatonin and urinary aMT6s levels. In summary, there was no evidence for circadian desynchronization associated with aging, but there was evidence of some rearrangement of the internal phase‐angles among the studied circadian rhythms.     

Effects of light on human circadian rhythms.

Blind subjects with defective retinal processing provide a good model to study the effects of light (or absence of light) on the human circadian system. The circadian rhythms (melatonin, cortisol, timing of sleep/wake) of individuals with different degrees of light perception (n = 67) have been studied. Blind subjects with some degree of light perception (LP) mainly have normally entrained circadian rhythms, whereas subjects with no conscious light perception (NPL) are more likely to exhibit disturbed circadian rhythms. All subjects who were bilaterally enucleated showed free running melatonin and cortisol rhythms. Studies assessing the light-induced suppression of melatonin show the response to be intensity and wavelength dependent. In contrast to ocular light exposure, extraocular light failed to suppress night-time melatonin. Thus, ocular light appears to be the predominant time cue and major determinant of circadian rhythm type. Optimisation of the light for entrainment (intensity, duration, wavelength, time of administration) requires further study.     

Can dim light melatonin onset be predicted by the timing of sleep in patients with possible circadian sleep-wake rhythm disorders?

Dim Light Melatonin Onset (DLMO) is a reliable marker of the endogenous circadian rhythm. To determine if sleep timing can predict DLMO, we investigated the relationship between sleep timing and DLMO in patients in various circadian sleep-wake rhythm disorders (CSWRDs), ages and genders. We found that correlations were only moderate between DLMO and sleep-onset in the complete data-set, but they increased in patients with delayed sleep-wake phase disorder (DSWPD), DSWPD patients with a regular sleep pattern and patients with advanced sleep-wake phase disorder (ASWPD); the levels of correlation were r = 0.542, 0.657, 0.728 and 0.814, respectively. In DSWPD patients with a regular sleep pattern, mid-sleep strongly correlated (r = 0.839) with DLMO. Correlation in other CSRWDs was not significant. DLMO, sleep-onset and age were most discriminated factors between the various CSRWDs. Estimation of DLMO is only possible in patients with ASWPD and in DSWPD patients with a regular sleep pattern.     

Effect of sleep deprivation on rhythms of clock gene expression and melatonin in humans

This study investigated the impact of sleep deprivation on the human circadian system. Plasma melatonin and cortisol levels and leukocyte expression levels of 12 genes were examined over 48?h (sleep vs. no-sleep nights) in 12 young males (mean?±?SD: 23?±?5 yrs). During one night of total sleep deprivation, BMAL1 expression was suppressed, the heat shock gene HSPA1B expression was induced, and the amplitude of the melatonin rhythm increased, whereas other high-amplitude clock gene rhythms (e.g., PER1-3, REV-ERBα) remained unaffected. These data suggest that the core clock mechanism in peripheral oscillators is compromised during acute sleep deprivation.     

The effect of cataract surgery on salivary melatonin and sleep quality in aging people

Blue light plays an important role in circadian photoentrainment by stimulating the melanopsin-expressing photosensitive retinal ganglion cells. Age-related cataract causes progressive loss of blue light transmission, which may lead to changes in circadian rhythm and sleep quality. In theory, increased light transmission by cataract surgery may improve circadian misalignment and sleep quality, while the effect of cataract surgery on circadian rhythm is not well understood. In this study, we assessed 30 binocular age-related nuclear cataract patients (aged 72.5 ± 7.2, 16 female) who were eligible for cataract surgery. All the patients underwent phacoemulsification cataract extraction and neutral ultraviolet-only blocking intraocular lens (IOLs) implantation. Visual functions including best-corrected visual acuity (BCVA), color perception and dark adaptation were assessed. Salivary samples were collected at 1-hour interval from 19:00 to 23:00 48 hours before and after surgery. Salivary melatonin concentration was measured and dim light melatonin onset (DLMO) was calculated subsequently. Sleep quality and daytime alertness were assessed before and a month after surgery using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). All the operated eyes demonstrated significant improvements in BCVA, color perception and dark adaptation after cataract surgery. Salivary melatonin concentration at 23:00 was significantly increased after surgery (P < 0.001). However, the average DLMO did not change significantly after surgery. In addition, PSQI and ESS scores were significantly decreased a month after surgery (P = 0.027, P < 0.001, respectively). In conclusion, cataract surgery promotes blue-light transmission; consequently, it may lead to the increase in nighttime melatonin concentration and improvement in sleep quality as well as daytime alertness.     

The Dim Light Melatonin Onset as a Marker for Orcadian Phase Position

Masking is known to affect a variety of circadian rhythms, making it difficult to use them as reliable markers of circadian phase position. Melatonin may be unique in that it appears to be masked only by (bright) light. Sleep and activity do not appear to influence the melatonin rhythm. By measuring the onset of melatonin production, a clearly demarcated event, we can reliably assess circadian phase position, provided blood is sampled under dim light (the dim light melatonin onset, or DL.MO). The DLMO has been useful in assessing the phase-shifting properties of bright light and in phase typing patients with chronobiologic disorders, such as winter depression.     

Changes in the diurnal rhythms of cortisol,melatonin, and testosterone after 2, 4, and 7 consecutive night shifts in male police officers

Night work is associated with a large range of acute health problems and possibly also health consequences in the long run. Yet, only very few field studies specifically investigate the effects of consecutive night shift on key physiological regulatory systems. In this field study, we investigated the effects of consecutive night shifts on three hormones, melatonin, cortisol, and testosterone, among police officers at work. More specifically, the aim was to investigate how the diurnal rhythms of melatonin, cortisol, and testosterone responded to two, four, and seven consecutive night shifts and a corresponding number of days for recovery. The study was part of the “In the Middle of the Night” project and included 73 male police officers from five different police districts. The participants were exposed to three intervention conditions: “2+2”: two consecutive night shifts followed by two consecutive day recovery days; “4+4”: four consecutive night shifts followed by four consecutive recovery days; “7+7”: seven consecutive night shifts followed by seven consecutive recovery days. On the last day with night shift and the last recovery day in each intervention, the participants collected saliva samples every 4th hour when awake. The diurnal rhythms of melatonin, cortisol, and testosterone were all affected differently by an increasing number of consecutive night shifts: the amplitude of the melatonin rhythm was suppressed by 4.9% per day (95% CI 1.4–8.2% per day; p = 0.006). The diurnal rhythm of cortisol phase was delayed with an increasing number of night shifts by 33 min/day (95% CI 18–48 min per day; p ≤ 0.001), but did not show any changes in amplitude. For the diurnal rhythm of testosterone, there was no effect of the number of consecutive night shifts and the diurnal rhythm completely followed the sleep/wake cycle. We found that there were no differences in the rhythms of melatonin, cortisol, and testosterone after 2, 4, and 7 recovery days, respectively. In conclusion, we found signs of desynchronization in terms of suppressed amplitude of melatonin and phase delay of salivary cortisol as a consequence of the increasing number of consecutive night shifts among police officers at work. Lack of synchronization has been suggested as a possible mechanism linking night work to disease, but this remains to be determined.     

The Effect of Traumatic Brain Injury on the Timing of Sleep

While there have been single case reports of the development of circadian rhythm sleep disorders, most commonly delayed sleep phase syndrome following traumatic brain injury (TBI), to our knowledge there have been no group investigations of changes to sleep timing in this population. The aim of the present study was to investigate sleep timing following TBI using the dim light melatonin onset (DLMO) as a marker of circadian phase and the Morningness‐Eveningness Questionnaire (MEQ) as a measure of sleep‐wake behavior. A sleep‐wake diary was also completed. It was hypothesized that the timing of DLMO would be delayed and that there would be a greater tendency toward eveningness on the MEQ in a post‐acute TBI group (n=10) compared to a gender and age matched control group. Participants were recruited at routine outpatient review appointments (TBI) and from the general population (control) as part of a larger study. They attended the sleep laboratory where questionnaires were completed, some retrospectively, and saliva melatonin samples were collected half‐hourly according to a standard protocol. The results show that the TBI and control groups reported similar habitual sleep times and this was reflected on the MEQ. There was, however, significant variability in the TBI group's change from the pre‐injury to the current MEQ score. The timing of melatonin onset was not different between the groups. While subtle changes (advances or delays) in this small sample may have cancelled each other out, the present study does not provide conclusive objective evidence of shift in circadian timing of sleep following TBI. Furthermore, although participants did report sleep timing changes, it is concluded that the MEQ may not be suitable for use with this cognitively impaired clinical group.     

REPEATED ASSESSMENT OF THE ENDOGENOUS 24-HOUR PROFILE OF BLOOD PRESSURE UNDER CONSTANT ROUTINE*

The impact of environmental and behavioral factors on the 24-h profile of blood pressure (BP) has been well established. Various attempts have been made to control these exogenous factors, in order to investigate a possible endogenous circadian variation of BP. Recently, we reported the results of the first environmentally and behaviorally controlled laboratory study with 24-h recordings of BP and heart rate (HR) during maintained wakefulness. In this constant-routine study, a pronounced endogenous circadian rhythm of HR was found, but circadian variation of BP was absent. This result suggested that the circadian rhythm of BP observed in earlier controlled studies, with sleep allowed, was evoked by the sleep–wake cycle as opposed to the endogenous circadian pacemaker. In order to verify our previous finding during maintained wakefulness, we repeated the experiment five times with six normotensive, healthy young subjects. Statistical analyses of the hourly measurements of BP and HR confirmed the replicable presence of an endogenous circadian rhythm of HR, as well as the consistent absence of an endogenous circadian variation of BP. Thus, this study provided additional evidence that the 24-h profile of BP—as observed under normal circumstances—is the sole result of environmental and behavioral factors such as the occurrence of sleep, and has no endogenous circadian component. (Chronobiology International, 18(1), 85–98, 2001)     

Late circadian phase in adults and children is correlated with use of high color temperature light at home at night

Light is the strongest synchronizer of human circadian rhythms, and exposure to residential light at night reportedly causes a delay of circadian rhythms. The present study was conducted to investigate the association between color temperature of light at home and circadian phase of salivary melatonin in adults and children. Twenty healthy children (mean age: 9.7 year) and 17 of their parents (mean age: 41.9 years) participated in the experiment. Circadian phase assessments were made with dim light melatonin onset (DLMO). There were large individual variations in DLMO both in adults and children. The average DLMO in adults and in children were 21:50 ± 1:12 and 20:55 ± 0:44, respectively. The average illuminance and color temperature of light at eye level were 139.6 ± 82.7 lx and 3862.0 ± 965.6 K, respectively. There were significant correlations between color temperature of light and DLMO in adults (r = 0.735, p < 0.01) and children (r = 0.479, p < 0.05), although no significant correlations were found between illuminance level and DLMO. The results suggest that high color temperature light at home might be a cause of the delay of circadian phase in adults and children.     

The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects

Exogenous melatonin (0.5-10 mg) has been shown to entrain the free-running circadian rhythms of some blind subjects. The aim of this study was to assess further the entraining effects of a daily dose of 0.5 mg melatonin on the cortisol rhythm and its acute effects on subjective sleep in blind subjects with free-running 6-sulphatoxymelatonin (aMT6s) rhythms (circadian period [tau] 24.23-24.95 h). Ten subjects (9 males) were studied, aged 32 to 65 years, with no conscious light perception (NPL). In a placebo-controlled, single-blind design, subjects received 0.5 mg melatonin or placebo p.o. daily at 2100 h (treatment duration 26-81 days depending on individuals' circadian period). Subjective sleep was assessed from daily sleep and nap diaries. Urinary cortisol and aMT6s were assessed for 24 to 48 h weekly and measured by radioimmunoassay. Seven subjects exhibited an entrained or shortened cortisol period during melatonin treatment. Of these, 4 subjects entrained with a period indistinguishable from 24 h, 2 subjects continued to free run for up to 25 days during melatonin treatment before their cortisol rhythm became entrained, and 1 subject appeared to exhibit a shortened cortisol period throughout melatonin treatment. The subjects who entrained within 7 days did so when melatonin treatment commenced in the phase advance portion of the melatonin PRC (CT6-18). When melatonin treatment ceased, cortisol and aMT6s rhythms free ran at a similar period to before treatment. Three subjects failed to entrain with initial melatonin treatment commencing in the phase delay portion of the PRC. During melatonin treatment, there was a significant increase in nighttime sleep duration and a reduction in the number and duration of daytime naps. The positive effect of melatonin on sleep may be partly due to its acute soporific properties. The findings demonstrate that a daily dose of 0.5 mg melatonin is effective at entraining the free-running circadian systems in most of the blind subjects studied, and that circadian time (CT) of administration of melatonin may be important in determining whether a subject entrains to melatonin treatment. Optimal treatment with melatonin for this non-24-h sleep disorder should correct the underlying circadian disorder (to entrain the sleep-wake cycle) in addition to improving sleep acutely.