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)     

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)     

Phase Delaying the Human Circadian Clock with Blue-Enriched Polychromatic Light

The human circadian system is maximally sensitive to short-wavelength (blue) light. In a previous study we found no difference between the magnitude of phase advances produced by bright white versus bright blue-enriched light using light boxes in a practical protocol that could be used in the real world. Since the spectral sensitivity of the circadian system may vary with a circadian rhythm, we tested whether the results of our recent phase-advancing study hold true for phase delays. In a within-subjects counterbalanced design, this study tested whether bright blue-enriched polychromatic light (17000 K, 4000 lux) could produce larger phase delays than bright white light (4100 K, 5000 lux) of equal photon density (4.2×10¹⁵ photons/cm²/sec). Healthy young subjects (n?=?13) received a 2 h phase delaying light pulse before bedtime combined with a gradually delaying sleep/dark schedule on each of 4 consecutive treatment days. On the first treatment day the light pulse began 3 h after the dim light melatonin onset (DLMO). An 8 h sleep episode began at the end of the light pulse. Light treatment and the sleep schedule were delayed 2 h on each subsequent treatment day. A circadian phase assessment was conducted before and after the series of light treatment days to determine the time of the DLMO and DLMOff. Phase delays in the blue-enriched and white conditions were not significantly different (DLMO: ?4.45±2.02 versus ?4.48±1.97 h; DLMOff: ?3.90±1.97 versus ?4.35±2.39 h, respectively). These results indicate that at light levels commonly used for circadian phase shifting, blue-enriched polychromatic light is no more effective than the white polychromatic lamps of a lower correlated color temperature (CCT) for phase delaying the circadian clock. (Author correspondence: ceastman@rush.edu)     

Differences in circadian phase and weekday/weekend sleep patterns in a sample of middle-aged morning types and evening types

Factors contributing to sleep timing and sleep restriction in daily life include chronotype and less flexibility in times available for sleep on scheduled days versus free days. There is some evidence that these two factors interact, with morning types and evening types reporting similar sleep need, but evening types being more likely to accumulate a sleep debt during the week and to have greater sleep extension on weekend nights. The aim of the present study was to evaluate the independent contributions of circadian phase and weekend-to-weekday variability to sleep timing in daily life. The study included 14 morning types and 14 evening types recruited from a community-based sample of New Zealand adults (mean age 41.1 ± 4.7 years). On days 1–15, the participants followed their usual routines in their own homes and daily sleep start, midpoint and end times were determined by actigraphy and sleep diaries. Days 16–17 involved a 17 h modified constant routine protocol in the laboratory (17:00 to 10:00, <20 lux) with half-hourly saliva samples assayed for melatonin. Mixed model ANCOVAs for repeated measures were used to investigate the independent relationships between sleep start and end times (separate models) and age (30–39 years versus 40–49 years), circadian phase [time of the dim light melatonin onset (DLMO)] and weekday/weekend schedules (Sunday–Thursday nights versus Friday–Saturday nights). As expected on weekdays, evening types had later sleep start times (mean = 23:47 versus 22:37, p < .0001) and end times (mean = 07:14 versus 05:56, p < .0001) than morning types. Similarly on weekend days, evening types had later sleep start times (mean = 00:14 versus 23:07, p = .0032) and end times (mean = 08:56 versus 07:04, p < .0001) than morning types. Evening types also had later DLMO (22:06 versus 20:46, p = .0002) than morning types (mean difference = 80.4 min, SE = 18.6 min). The ANCOVA models found that later sleep start times were associated with later DLMO (p = .0172) and weekend-to-weekday sleep timing variability (p < .0001), after controlling for age, while later sleep end times were associated with later DLMO (p = .0038), younger age (p = .0190) and weekend days (p < .0001). Sleep end times showed stronger association with DLMO (for every 30 min delay in DLMO, estimated mean sleep end time occurred 14.0 min later versus 10.19 min later for sleep start times). Sleep end times also showed greater delays on weekends versus weekdays (estimated mean delay for sleep end time = 84 min, for sleep start time = 28 min). Comparing morning types and evening types, the estimated contributions of the DLMO to the mean observed differences in sleep timing were on weekdays, 39% for sleep start times and 49% for sleep end times; and on weekends, 41% for sleep start times and 34% of sleep end times. We conclude that differences in sleep timing between morning types and evening types were much greater than would be predicted on the basis of the independent contribution of the difference in DLMO on both weekdays and weekend days. The timing of sleep in daily life involves complex interactions between physiological and psychosocial factors, which may be moderated by age in adults aged 30–49 years.     

Photic Resetting in Night-Shift Work: Impact on Nurses' Sleep

The objective of this study was to quantify daytime sleep in night-shift workers with and without an intervention designed to recover the normal relationship between the endogenous circadian pacemaker and the sleep/wake cycle. Workers of the treatment group received intermittent exposure to full-spectrum bright light during night shifts and wore dark goggles during the morning commute home. All workers maintained stable 8-h daytime sleep/darkness schedules. The authors found that workers of the treatment group had daytime sleep episodes that lasted 7.1?±?.1?h (mean?±?SEM) versus 6.6?±?.2?h for workers in the control group (p?=?.04). The increase in total sleep time co-occurred with a larger proportion of the melatonin secretory episode during daytime sleep in workers of the treatment group. The results of this study showed reestablishment of a phase angle that is comparable to that observed on a day-oriented schedule favors longer daytime sleep episodes in night-shift workers. (Author correspondence: diane.boivin@douglas.mcgill.ca)     

EVENING DAYLIGHT MAY CAUSE ADOLESCENTS TO SLEEP LESS IN SPRING THAN IN WINTER

Sleep restriction commonly experienced by adolescents can stem from a slower increase in sleep pressure by the homeostatic processes and from phase delays of the circadian system. With regard to the latter potential cause, the authors hypothesized that because there is more natural evening light during the spring than winter, a sample of adolescent students would be more phase delayed in spring than in winter, would have later sleep onset times, and because of fixed school schedules would have shorter sleep durations. Sixteen eighth-grade subjects were recruited for the study. The authors collected sleep logs and saliva samples to determine their dim light melatonin onset (DLMO), a well-established circadian marker. Actual circadian light exposures experienced by a subset of 12 subjects over the course of 7 days in winter and in spring using a personal, head-worn, circadian light measurement device are also reported here. Results showed that this sample of adolescents was exposed to significantly more circadian light in spring than in winter, especially during the evening hours when light exposure would likely delay circadian phase. Consistent with the light data, DLMO and sleep onset times were significantly more delayed, and sleep durations were significantly shorter in spring than in winter. The present ecological study of light, circadian phase, and self-reported sleep suggests that greater access to evening daylight in the spring may lead to sleep restriction in adolescents while attending school. Therefore, lighting schemes that reduce evening light in the spring may encourage longer sleep times in adolescents. (Author correspondence: figuem@rpi.edu)     

Mood,Alertness, and Performance in Response to Sleep Deprivation and Recovery Sleep in Experienced Shiftworkers Versus Non-Shiftworkers

Previous studies have shown increased sleepiness and mood changes in shiftworkers, which may be due to sleep deprivation or circadian disruption. Few studies, however, have compared responses of experienced shiftworkers and non-shiftworkers to sleep deprivation in an identical laboratory setting. The aim of this laboratory study, therefore, was to compare long-term shiftworkers and non-shiftworkers and to investigate the effects of one night of total sleep deprivation (30.5?h of continuous wakefulness) and recovery sleep on psychomotor vigilance, self-rated alertness, and mood. Eleven experienced male shiftworkers (shiftwork ≥5 yrs) were matched with 14 non-shiftworkers for age (mean?±?SD: 35.7?±?7.2 and 32.5?±?6.2 yrs, respectively) and body mass index (BMI) (28.7?±?3.8 and 26.6?±?3.4?kg/m², respectively). After keeping a 7-d self-selected sleep/wake cycle (7.5/8?h nocturnal sleep), both groups entered a laboratory session consisting of a night of adaptation sleep and a baseline sleep (each 7.5/8?h), a sleep deprivation night, and recovery sleep (4-h nap plus 7.5/8?h nighttime sleep). Subjective alertness and mood were assessed with the Karolinska Sleepiness Scale (KSS) and 9-digit rating scales, and vigilance was measured by the visual psychomotor vigilance test (PVT). A mixed-model regression analysis was carried out on data collected every hour during the sleep deprivation night and on all days (except for the adaptation day), at .25, 4.25, 5.25, 11.5, 12.5, and 13.5?h after habitual wake-up time. Despite similar circadian phase (melatonin onset), demographics, food intake, body posture, and environmental light, shiftworkers felt significantly more alert, more cheerful, more elated, and calmer than non-shiftworkers throughout the laboratory study. In addition, shiftworkers showed a faster median reaction time (RT) compared to non-shiftworkers, although four other PVT parameters did not differ between the groups. As expected, both groups showed a decrease in subjective alertness and PVT performance during and following the sleep deprivation night. Subjective sleepiness and most aspects of PVT performance returned to baseline levels after a nap and recovery sleep. The mechanisms underlying the observed differences between shiftworkers and non-shiftworkers require further study, but may be related to the absence of shiftwork the week prior to and during the laboratory study as well as selection into and out of shiftwork. (Author correspondence: sophie.wehrens@surrey.ac.uk)     

PHASE RELATIONSHIP BETWEEN SKIN TEMPERATURE AND SLEEP-WAKE RHYTHMS IN WOMEN WITH VASCULAR DYSREGULATION AND CONTROLS UNDER REAL-LIFE CONDITIONS

The aim of the study was to investigate whether women with primary vascular dysregulation (VD; main symptoms of thermal discomfort with cold extremities) and difficulties initiating sleep (DIS) exhibit a disturbed phase of entrainment (Ψ) under everyday life conditions. The authors predicted a phase delay of the distal-proximal skin temperature gradient and salivary melatonin rhythms with respect to the sleep-wake cycle in women with VD and DIS (WVD) compared to controls (CON), similar to that found in their previous constant-routine laboratory data. A total of 41 young healthy women, 20 with WVD and 21 matched CON without VD and normal sleep onset latency (SOL), were investigated under ambulatory conditions (following their habitual bedtimes) during 7 days of continuous recording of skin temperatures, sleep-wake cycles monitored by actimetry and sleep-wake diaries, and single evening saliva collections for determining the circadian marker of dim light melatonin onset (DLMO). Compared to CON, WVD showed increased distal vasoconstriction at midday and in the evening, as indicated by lower distal (DIST; hands and feet) and foot-calf skin temperatures, and distal-proximal skin temperature gradients (p?<?.05). WVD manifested distal vasoconstriction before lights-off that also lasted longer after lights-off than in CON. In parallel, WVD exhibited a longer SOL (p?<?.05). To define internal phase-relationships, cross-correlation analyses were performed using diurnal rhythms of wrist activity and foot skin temperature. WVD showed a phase delay in foot skin temperature (CON versus WVD: 3.57?±?17.28?min versus 38.50?±?16.65?min; p?<?.05) but not in wrist activity. This finding was validated by additional within-subject cross-correlation analyses using the diurnal wrist activity pattern as reference. DLMO and habitual sleep times did not differ between CON and WVD. The authors conclude that WVD exhibit a phase delay of distal vasodilatation with respect to their habitual sleep-wake cycle and other circadian phase markers, such as DLMO. A full factorial design will have to show whether the finding is specific to primary vascular dysregualtion, to DIS, or to their interaction. (Author correspondence: Kurt.kraeuchi@upkbs.ch)     

Eveningness,Sleep Patterns,Daytime Functioning,and Quality of Life in Israeli Adolescents

The purpose of the study was to assess the relationships between eveningness, sleep patterns, measures of daytime functioning, i.e., sleepiness, sleep problem behaviors, and depressed mood, and quality of life (QOL) in young Israeli adolescents. A cross-sectional survey was performed in urban and rural middle schools in Northern Israel. Participants were 470 eighth and ninth grade middle school students (14?±?0.8 yrs of age) in the normative school system. Students completed the modified School Sleep Habits Survey (SSHS) and Pediatric Quality of Life Inventory Short Form, assessing six subscales of physical, emotional, social, school performance, and psychosocial functioning, plus an addition generated total score. During weekdays and weekends, evening types went to bed later, their sleep latency was longer, their wake-up time was later, and their sleep duration was shorter than intermediate and morning types. Evening types exhibited more sleep problem behaviors, sleepiness, depressed mood, and lower QOL compared to intermediate and morning types. Based on the regression model, sleepiness, sleep-problem behaviors, and depressed mood were the variables most strongly associated with QOL, followed by morning-evening preference, weekday sleep duration, and weekend sleep latency. This study is the first to assess QOL in normative, healthy adolescents and to demonstrate strong associations between morning-evening preference and QOL. These findings enhance the need to identify young individuals with an evening preference, and to be aware of the characteristics and manifestations of the evening chronotype on daytime and nighttime behaviors in adolescence. (Author correspondence: Orna@yvc.ac.il)     

Circadian misalignment and weekend alcohol use in late adolescent drinkers: preliminary evidence

Alcohol use accelerates during late adolescence, predicting the development of alcohol use disorders (AUDs) and other negative outcomes. Identifying modifiable risk factors for alcohol use during this time could lead to novel prevention approaches. Burgeoning evidence suggests that sleep and circadian factors are cross-sectionally and longitudinally linked to alcohol use and problems, but more proximal relationships have been understudied. Circadian misalignment, in particular, is hypothesized to increase the risk for AUDs, but almost no published studies have included a biological measure of misalignment. In the present study, we aimed to extend existing research by assessing the relationship between adolescent circadian misalignment and alcohol use on a proximal timeframe (over two weeks) and by including three complementary measures of circadian alignment. We studied 36 healthy late (18–22 years old, 22 females) alcohol drinkers (reporting ≥1, standard drink per week over the past 30 days) over 14 days. Throughout the study, participants reported prior day’s alcohol use and prior night’s sleep each morning via smartphone and a secure, browser-based interface. Circadian phase was assessed via the dim light melatonin onset (DLMO) in the laboratory on two occasions (Thursday and Sunday nights) in counterbalanced order. The three measures of circadian alignment included DLMO-midsleep interval, “classic” social jet lag (weekday-weekend difference in midsleep), and “objective” social jet lag (weekday-weekend difference in DLMO). Multivariate imputation by chained equations was used to impute missing data, and Poisson regression models were used to assess associations between circadian alignment variables and weekend alcohol use. Covariates included sex, age, Thursday alcohol use, and Thursday sleep characteristics. As predicted, greater misalignment was associated with greater weekend alcohol use for two of the three alignment measures (shorter DLMO-midsleep intervals and larger weekday-weekend differences in midsleep), while larger weekday-weekend differences in DLMO were associated with less alcohol use. Notably, in contrast to expectations, the distribution of weekday-weekend differences in DLMO was nearly equally distributed between individuals advancing over the weekend and those delaying over the weekend. This unexpected finding plausibly reflects the fact that college students are not subject to the same systematically earlier weekday schedules observed in high school students and working adults. These preliminary findings support the need for larger, more definitive studies investigating the proximal relationships between circadian alignment and alcohol use among late adolescents.     

An Improved Method for Estimating Human Circadian Phase Derived From Multichannel Ambulatory Monitoring and Artificial Neural Networks

Recently, we developed a novel method for estimating human circadian phase with noninvasive ambulatory measurements combined with subject-independent multiple regression models and a curve-fitting approach. With this, we were able to estimate circadian phase under real-life conditions with low subject burden, i.e., without need of constant routine (CR) laboratory conditions, and without measuring standard circadian markers, such as core body temperature (CBT) or pineal hormone melatonin rhythms. The precision of ambulatory-derived estimated circadian phase was within an error of 12?±?41?min (mean?±?SD) in comparison to melatonin phase during a CR protocol. The physiological measures could be reduced to a triple combination: skin temperatures, irradiance in the blue spectral band of ambient light, and motion acceleration. Here, we present a nonlinear regression model approach based on artificial neural networks for a larger data set (25 healthy young males), including both the original data and additional data collected in the same protocol and using the same equipment. Throughout our validation study, subjects wore multichannel ambulatory monitoring devices and went about their daily routine for 1 wk. The devices collected a large number of physiological, behavioral, and environmental variables, including CBT, skin temperatures, cardiovascular and respiratory functions, movement/posture, ambient temperature, spectral composition and intensity of light perceived at eye level, and sleep logs. After the ambulatory phase, study volunteers underwent a 32-h CR protocol in the laboratory for measuring unmasked circadian phase (i.e., “midpoint” of the nighttime melatonin rhythm). To overcome the complex masking effects of many different confounding variables during ambulatory measurements, neural network–based nonlinear regression techniques were applied in combination with the cross-validation approach to subject-independent prediction of circadian phase. The most accurate estimate of circadian phase with a prediction error of ?3?±?23?min (mean?±?SD) was achieved using only two types of the measured variables: skin temperatures and irradiance for ambient light in the blue spectral band. Compared to our previous linear multiple regression modeling approach, motion acceleration data can be excluded and prediction accuracy, nevertheless, improved. Neural network regression showed statistically significant improvement of variance of prediction error over traditional approaches in determining circadian phase based on single predictors (CBT, motion acceleration, or sleep logs), even though none of these variables was included as predictor. We, therefore, have identified two sets of noninvasive measures that, combined with the prediction model, can provide researchers and clinicians with a precise measure of internal time, in spite of the masking effects of daily behavior. This method, here validated in healthy young men, requires testing in a clinical or shiftwork population suffering from circadian sleep-wake disorders. (Author correspondence: vitaliy.kolodyazhniy@sbg.ac.at)     

Diurnal Variation in Vascular Function: Role of Sleep

Although vascular function is lower in the morning than afternoon, previous studies have not assessed the influence of prior sleep on this diurnal variation. The authors employed a semiconstant routine protocol to study the contribution of prior nocturnal sleep to the previously observed impairment in vascular function in the morning. Brachial artery vascular function was assessed using the flow-mediated dilation technique (FMD) in 9 healthy, physically active males (mean?±?SD: 27?±?9 yrs of age), at 08:00 and 16:00?h following, respectively, 3.29?±?.37 and 3.24?±?.57?h prior sleep estimated using actimetry. Heart rate and systolic and diastolic blood pressures were also measured. The data of the experimental sleep condition were compared with the data of the “normal” diurnal sleep condition, in which FMD measurements were obtained from 21 healthy individuals who slept only during the night, as usual, before the morning test session. The morning-afternoon difference in FMD was 1?±?4% in the experimental sleep condition compared with 3?±?4% in the normal sleep condition (p?=?.04). This difference was explained by FMD being 3?±?3% lower in afternoon following the prior experimental sleep (p?=?.01). These data suggest that FMD is more dependent on the influence of supine sleep than the endogenous circadian timekeeper, in agreement with our previous finding that diurnal variation in FMD is influenced by exercise. These findings also raise the possibility of a lower homeostatic “set point” for vascular function following a period of sleep and in the absence of perturbing hemodynamic fluctuation. (Author correspondence: h.jones1@ljmu.ac.uk)     

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 (R²?=?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. (Author correspondence: mdittmar@zoologie.uni-kiel.de)     

Idiopathic chronic sleep onset insomnia in attention-deficit/hyperactivity disorder: a circadian rhythm sleep disorder

To investigate whether ADHD-related sleep-onset insomnia (SOI) is a circadian rhythm disorder, we compared actigraphic sleep estimates, the circadian rest-activity rhythm, and dim light melatonin onset (DLMO) in ADHD children having chronic idiopathic SOI with that in ADHD children without sleep problems. Participants were 87 psychotropic-medication-na?ve children, aged 6 to 12 yrs, with rigorously diagnosed ADHD and SOI (ADHD-SOI) and 33 children with ADHD without SOI (ADHD-noSOI) referred from community mental health institutions and pediatric departments of non-academic hospitals in The Netherlands. Measurements were 1 wk, 24 h actigraphy recordings and salivary DLMO. The mean (+/-SD) sleep onset time was 21:38 +/- 0:54 h in ADHD-SOI, which was significantly (p < 0.001) later than that of 20:49 +/- 0:49 h in ADHD-noSOI. DLMO was significantly later in ADHD-SOI (20:32 +/- 0:55 h), compared with ADHD-noSOI (19:47 +/- 0:49 h; p < 0.001). Wake-up time in ADHD-SOI was later than in ADHD-noSOI (p = 0.002). There were no significant between-group differences in sleep maintenance, as estimated by number of wake bouts and activity level in the least active 5 h period, or inter- and intradaily rhythm variability. We conclude that children with ADHD and chronic idiopathic sleep-onset insomnia show a delayed sleep phase and delayed DLMO, compared with ADHD children without SOI.     

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).     

Sleep Restriction Masks the Influence of the Circadian Process on Sleep Propensity

Previous forced desynchrony studies have highlighted the close relationship between the circadian rhythms of core body temperature (CBT) and sleep propensity. In particular, these studies have shown that a “forbidden zone” for sleep exists on the rising limb of the CBT rhythm. In these previous studies, the length of the experimental day was either ultrashort (90?min), short (20?h), or long (28?h), and the ratio of sleep to wake was normal (i.e., 1:2). The aim of the current study was to examine the relative effects of the circadian and homeostatic processes on sleep propensity using a 28-h forced desynchrony protocol in which the ratio of sleep to wake was substantially lower than normal (i.e., 1:5). Twenty-seven healthy males lived in a time-isolation sleep laboratory for 11 consecutive days. Participants completed either a control (n?=?13) or sleep restriction (n?=?14) condition. In both conditions, the protocol consisted of 2?×?24-h baseline days followed by 8?×?28-h forced desynchrony days. On forced desynchrony days, the control group had 9.3?h in bed and 18.7?h of wake, and the sleep restriction group had 4.7?h in bed and 23.3?h of wake. For all participants, each 30-s epoch of time in bed was scored as sleep or wake based on standard polysomnography recordings, and was also assigned a circadian phase (360°?=?24?h) based on a cosine equation fitted to continuously recorded CBT data. For each circadian phase (i.e., 72?×?5° bins), sleep propensity was calculated as the percentage of epochs spent in bed scored as sleep. For the control group, there was a clear circadian rhythm in sleep propensity, with a peak of 98.5% at 5° (～05:20?h), a trough of 64.9% at 245° (～21:20?h), and an average of 82.3%. In contrast, sleep propensity for the sleep restriction group was relatively high at all circadian phases, with an average of 96.7%. For this group, the highest sleep propensity (99.0%) occurred at 60° (～09:00?h), and the lowest sleep propensity (91.3%) occurred at 265° (～22:40?h). As has been shown previously, these current data indicate that with a normal sleep-to-wake ratio, the effect of the circadian process on sleep propensity is pronounced, such that a forbidden zone for sleep exists at a phase equivalent to evening time for a normally entrained individual. However, these current data also indicate that when the ratio of sleep to wake is substantially lower than normal, this circadian effect is masked. In particular, sleep propensity is very high at all circadian phases, including those that coincide with the forbidden zone for sleep. This finding suggests that if the homeostatic pressure for sleep is sufficiently high, then the circadian drive for wakefulness can be overridden. In future studies, it will be important to determine whether or not this masking effect occurs with less severe sleep restriction, e.g., with a sleep-to-wake ratio of 1:3. (Author correspondence: charli.sargent@cqu.edu.au)     

Ring the Bell for Matins: Circadian Adaptation to Split Sleep by Cloistered Monks and Nuns

Cloistered monks and nuns adhere to a 10-century-old strict schedule with a common zeitgeber of a night split by a 2- to 3-h-long Office (Matins). The authors evaluated how the circadian core body temperature rhythm and sleep adapt in cloistered monks and nuns in two monasteries. Five monks and five nuns following the split-sleep night schedule for 5 to 46 yrs without interruption and 10 controls underwent interviews, sleep scales, and physical examination and produced a week-long sleep diary and actigraphy, plus 48-h recordings of core body temperature. The circadian rhythm of temperature was described by partial Fourier time-series analysis (with 12- and 24-h harmonics). The temperature peak and trough values and clock times did not differ between groups. However, the temperature rhythm was biphasic in monks and nuns, with an early decrease at 19:39?±?4:30?h (median?±?95% interval), plateau or rise of temperature at 22:35?±?00:23?h (while asleep) lasting 296?±?39?min, followed by a second decrease after the Matins Office, and a classical morning rise. Although they required alarm clocks to wake-up for Matins at midnight, the body temperature rise anticipated the nocturnal awakening by 85?±?15?min. Compared to the controls, the monks and nuns had an earlier sleep onset (20:05?±?00:59?h vs. 00:00?±?00:54?h, median?±?95% confidence interval, p?=?.0001) and offset (06:27?±?0:22?h, vs. 07:37?±?0:33?h, p?=?.0001), as well as a shorter sleep time (6.5?±?0.6 vs. 7.6?±?0.7?h, p?=?.05). They reported difficulties with sleep latency, sleep duration, and daytime function, and more frequent hypnagogic hallucinations. In contrast to their daytime silence, they experienced conversations (and occasionally prayers) in dreams. The biphasic temperature profile in monks and nuns suggests the human clock adapts to and even anticipates nocturnal awakenings. It resembles the biphasic sleep and rhythm of healthy volunteers transferred to a short (10-h) photoperiod and provides a living glance into the sleep pattern of medieval time. (Author correspondence: isabelle.arnulf@psl.aphp.fr)     

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.