The effects of thoracic and cervical spinal cord lesions on the circadian rhythm of core body temperature

Individuals with a spinal cord injury (SCI) have compromised afferent and efferent information below the lesion. Intact afferent information regarding skin temperature and the ability to regulate skin blood flow lead to an altered heat balance, which may impact the circadian variation in core body temperature (Tcore) and sleep-wake cycle. The authors assessed the circadian variation of Tcore in SCI individuals and able-bodied controls matched for the timing of the sleep-wake cycle. The authors examined subjects who had a high (cervical) or a low (thoracic) lesion. Intestinal Tcore (telemetry system) and physical activity (ambulatory activity monitor) levels were measured continuously and simultaneously in 8 tetraplegics, 7 paraplegics, and 8 able-bodied controls during one 24-h period of "normal" living. The regression slope between activity and Tcore was also calculated for each 2-h bin. Circadian rhythm parameters were estimated with partial Fourier time-series analysis, and groups were compared with general linear models, adjusted for the influence of individual wake-time. The (mean ± SD) dominant period length for controls, paraplegics, and tetraplegics were 24.4 ± 5.4 h, 22.5 ± 5.0 h, and 16.5 ± 5.1 h, respectively (p =?.02). A significantly more pronounced 8-h harmonic was found for the variation in Tcore of SCI individuals (p = .05). Tetraplegics showed the highest nocturnal mean Tcore (p = .005), a 5-h phase-advanced circadian trough time (p = .04), and more variable relationships between physical activity and Tcore (p = .03). Taken together, tetraplegics demonstrate a pronounced disturbance of the circadian variation of Tcore, whereas the variation of Tcore in paraplegics was comparable to able-bodied controls.     

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)     

HYPOCRETIN DEFICIENCY IN NARCOLEPSY WITH CATAPLEXY IS ASSOCIATED WITH A NORMAL BODY CORE TEMPERATURE MODULATION

Narcolepsy with cataplexy (NC) is a sleep disorder caused by the loss of the hypothalamic neurons producing hypocretin. The clinical hallmarks of the disease are excessive daytime sleepiness, cataplexy, other rapid eye movement (REM) sleep phenomena, and a fragmented wake-sleep cycle. Experimental data suggest that the hypocretin system is involved primarily in the circadian timing of sleep and wakefulness but also in the control of other biological functions such as thermoregulation. The object of this study was to determine the effects of the hypocretin deficit and of the wake-sleep cycle fragmentation on body core temperature (BcT) modulation in a sample of drug-free NC patients under controlled conditions. Ten adult NC patients with low cerebrospinal fluid (CSF) hypocretin levels (9 men; age: 38?±?12 yrs) were compared with 10 healthy control subjects (7 men; age: 44.9?±?12 yrs). BcT and sleep-wake cycle were continuously monitored for 44?h from 12:00?h. During the study, subjects were allowed to sleep ad libitum, living in a temperature- and humidity-controlled room, lying in bed except when eating, in a light-dark schedule (dark [D] period: 23:00–07:00?h). Sleep structure was analyzed over the 24-h period, the light (L) and the D periods. The wake-sleep cycle fragmentation was determined by calculating the frame-shift index (number of 30-s sleep stage shifts occurring every 15?min) throughout the 44-h study. The analysis of BcT circadian rhythmicity was performed according to the single cosinor method. The time-course changes in BcT and in frame-shift index were compared between narcoleptics and controls by testing the time?×?group (controls versus NC subjects) interaction effect. The state-dependent analysis of BcT during D was performed by fitting a mixed model where the factors were wake-sleep phases (wake, NREM stages 1 and 2, slow-wave sleep, and REM sleep) and group. The results showed that NC patients slept significantly more than controls during the 24?h due to a higher representation of any sleep stage (p?<?.001) during L, whereas the total amount of night sleep and its architecture were comparable in the two groups. Wake-sleep fragmentation was higher (p?<?.001) in NC subjects especially during L. Despite these differences, mesor (24-h mean), amplitude, and acrophase (peak time) of BcT circadian rhythm were comparable in narcoleptics and controls, and no between-group differences were detected in the time-course changes and in the state-dependent modulation at night of BcT. These data indicate that the hypocretin deficit in drug-free NC patients and their altered wake-sleep cycle couple with an intact modulation of BcT. (Author correspondence: daniela.grimaldi@unibo.it)     

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)     

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)     

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)     

Time Course of Neurobehavioral Alertness During Extended Wakefulness in Morning- and Evening-Type Healthy Sleepers

The aim of the study was to evaluate the influence of chronotype (morning-type versus evening-type) living in a fixed sleep-wake schedule different from one's preferred sleep schedules on the time course of neurobehavioral performance during controlled extended wakefulness. The authors studied 9 morning-type and 9 evening-type healthy male subjects (21.4?±?1.9 yrs). Before the experiment, all participants underwent a fixed sleep-wake schedule mimicking a regular working day (bedtime: 23:30?h; wake time: 07:30?h). Then, following two nights in the laboratory, both chronotypes underwent a 36-h constant routine, performing a cognitive test of sustained attention every hour. Core body temperature, salivary melatonin secretion, objective alertness (maintenance of wakefulness test), and subjective sleepiness (visual analog scale) were also assessed. Evening-types expressed a higher level of subjective sleepiness than morning types, whereas their objective levels of alertness were not different. Cognitive performance in the lapse domain remained stable during the normal waking day and then declined during the biological night, with a similar time course for both chronotypes. Evening types maintained optimal alertness (i.e., 10% fastest reaction time) throughout the night, whereas morning types did not. For both chronotypes, the circadian performance profile was correlated with the circadian subjective somnolence profile and was slightly phase-delayed with melatonin secretion. Circadian performance was less correlated with circadian core body temperature. Lapse domain was phase-delayed with body temperature (2–4?h), whereas optimal alertness was slightly phase-delayed with body temperature (1?h). These results indicate evening types living in a fixed sleep-wake schedule mimicking a regular working day (different from their preferred sleep schedules) express higher subjective sleepiness but can maintain the same level of objective alertness during a normal waking day as morning types. Furthermore, evening types were found to maintain optimal alertness throughout their nighttime, whereas morning types could not. The authors suggest that evening-type subjects have a higher voluntary engagement of wake-maintenance mechanisms during extended wakefulness due to adaptation of their sleep-wake schedule to social constraints. (Author correspondence: jack.taillard@gmail.com)     

CARDIOVASCULAR RHYTHMS AND CARDIAC BAROREFLEX SENSITIVITY IN AT1A RECEPTOR GAIN-OF-FUNCTION MUTANT MICE

A mutant mouse expressing a gain-of-function of the AT_1A angiotensin II receptor was engineered to study the consequences of a constitutive activation of this receptor on blood pressure (BP). Cardiovascular rhythms and spontaneous cardiac baroreflex sensitivity (BRS) were evaluated using telemetric BP recordings of five transgenic (AT_1AMUT) and five wild (AT_1AWT) mice. The circadian rhythms were described with the Chronos-Fit program. The gain of the transfer function between systolic BP (SBP) and pulse intervals used to estimate the spontaneous BRS (ms/mmHg) was calculated in the low frequency (0.15–0.60?Hz) band. Transgenic AT_1AMUT exhibited higher BP and heart rate (HR) levels compared to controls (SBP AT_1AMUT 134.6?±?5.9?mmHg vs. AT_1AWT 110.5?±?5.9; p?<?0.05; HR AT_1AMUT 531.0?±?14.9 vs. AT_1AWT 454.8?±?5.4 beats/min; p?=?0.001). Spontaneous BRS was diminished in transgenic mice (AT_1AMUT 1.23?±?0.17?ms/mmHg vs. AT_1AWT 1.91?±?0.18?ms/mmHg; p?<?0.05). Motor activity did not differ between groups. These variables exhibited circadian changes, and the differences between the strains were maintained throughout the cycle. The highest values for BP, HR, and locomotor activity were observed at night. Spontaneous BRS varied in the opposite direction, with the lowest gain estimated when BP and HR were elevated (i.e., at night, when the animals were active). It is likely the BP elevation of the mutant mice results from the amplification of the effects of AngII at different sites. Future studies are necessary to explore whether AT_1A receptor activation at the central nervous system level effectively contributed to the observed differences. (Author correspondence: jean-luc.elghozi@nck.aphp.fr)     

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)     

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)     

Young Women With Major Depression Live on Higher Homeostatic Sleep Pressure Than Healthy Controls

There is mounting evidence for the involvement of the sleep-wake cycle and the circadian system in the pathogenesis of major depression. However, only a few studies so far focused on sleep and circadian rhythms under controlled experimental conditions. Thus, it remains unclear whether homeostatic sleep pressure or circadian rhythms, or both, are altered in depression. Here, the authors aimed at quantifying homeostatic and circadian sleep-wake regulatory mechanisms in young women suffering from major depressive disorder and healthy controls during a multiple nap paradigm under constant routine conditions. After an 8-h baseline night, 9 depressed women, 8 healthy young women, and 8 healthy older women underwent a 40-h multiple nap protocol (10 short sleep-wake cycles) followed by an 8-h recovery night. Polysomnographic recordings were done continuously, and subjective sleepiness was assessed. In order to measure circadian output, salivary melatonin samples were collected during scheduled wakefulness, and the circadian modulation of sleep spindles was analyzed with reference to the timing of melatonin secretion. Sleep parameters as well as non-rapid eye movement (NREM) sleep electroencephalographic (EEG) spectra were determined for collapsed left, central, and right frontal, central, parietal, and occipital derivations for the night and nap-sleep episodes in the frequency range .75–25?Hz. Young depressed women showed higher frontal EEG delta activity, as a marker of homeostatic sleep pressure, compared to healthy young and older women across both night sleep episodes together with significantly higher subjective sleepiness. Higher delta sleep EEG activity in the naps during the biological day were observed in young depressed women along with reduced nighttime melatonin secretion as compared to healthy young volunteers. The circadian modulation of sleep spindles between the biological night and day was virtually absent in healthy older women and partially impaired in young depressed women. These data provide strong evidence for higher homeostatic sleep pressure in young moderately depressed women, along with some indications for impairment of the strength of the endogenous circadian output signal involved in sleep-wake regulation. This finding may have important repercussions on the treatment of the illness as such that a selective suppression of EEG slow-wave activity could promote acute mood improvement. (Author correspondence: Christian.cajochen@upkbs.ch)     

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)     

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)     

Phototherapy and Orange-Tinted Goggles for Night-Shift Adaptation of Police Officers on Patrol

The aim of the present combined field and laboratory study was to assess circadian entrainment in two groups of police officers working seven consecutive 8/8.5-h night shifts as part of a rotating schedule. Eight full-time police officers on patrol (mean age?±?SD: 29.8?±?6.5 yrs) were provided an intervention consisting of intermittent exposure to wide-spectrum bright light at night, orange-tinted goggles at sunrise, and maintenance of a regular sleep/darkness episode in the day. Orange-tinted goggles have been shown to block the melatonin-suppressing effect of light significantly more than neutral gray density goggles. Nine control group police officers (mean age?±?SD: 30.3?±?4.1 yrs) working the same schedule were enrolled. Police officers were studied before, after (in the laboratory), and during (ambulatory) a series of seven consecutive nights. Urine samples were collected at wake time and bedtime throughout the week of night work and during laboratory visits (1?×?/3?h) preceding and following the work week to measure urinary 6-sulfatoxymelatonin (UaMT6s) excretion rate. Subjective alertness was assessed at the start, middle, and end of night shifts. A 10-min psychomotor vigilance task was performed at the start and end of each shift. Both laboratory visits consisted of two 8-h sleep episodes based on the prior schedule. Saliva samples were collected 2?×?/h during waking episodes to assay their melatonin content. Subjective alertness (3?×?/h) and performance (1?×?/2?h) were assessed during wake periods in the laboratory. A mixed linear model was used to analyze the progression of UaMt6s excreted during daytime sleep episodes at home, as well as psychomotor performance and subjective alertness during night shifts. Two-way analysis of variance (ANOVA) (factors: laboratory visit and group) were used to compare peak salivary melatonin and UaMT6s excretion rate in the laboratory. In both groups of police officers, the excretion rate of UaMT6s at home was higher during daytime sleep episodes at the end compared to the start of the work week (p?<?.001). This rate increased significantly more in the intervention than control group (p?=?.032). A significant phase delay of salivary melatonin was observed in both groups at the end of study (p?=?.009), although no significant between-group difference was reached. Reaction speed dropped, and subjective alertness decreased throughout the night shift in both groups (p?<?.001). Reaction speed decreased throughout the work week in the control group (p?≤?.021), whereas no difference was observed in the intervention group. Median reaction time was increased as of the 5th and 6th nights compared to the 2nd night in controls (p?≤?.003), whereas it remained stable in the intervention group. These observations indicate better physiological adaptation in the intervention group compared to the controls. (Author correspondence: diane.boivin@douglas.mcgill.ca)     

HEART-RATE VARIABILITY IN WOMEN DURING 40-HOUR PROLONGED WAKEFULNESS

Heart-rate variability patterns of 18 women during a 40-h constant routine of prolonged wakefulness under controlled laboratory conditions were analyzed. The authors tested the circadian timing of the autonomic nervous system and the relationship between the sympathetic and vagal branches in women with both a functional disorder of vascular regulation (main symptom: cold hands and feet) and prolonged sleep onset and controls without these symptoms. Spectral analysis of R-R intervals during paced breathing episodes revealed significantly lower power values in the high-frequency band (HF; 0.15–0.4?Hz) but not in the low-frequency band (LF; 0.04–0.15?Hz), leading to a significantly elevated LF/HF ratio in the former group. A significant circadian rhythm in LF power and heart rate occurred in both groups, and a significant correlation was found between sleepiness and sympathovagal balance (r?=?.53, p?<?.05). These findings indicate not only an autonomic imbalance in the first group compared with controls, but also two strategies of the autonomic nervous system to fight against fatigue in women. One implies circadian control and the other homeostatic control, and both are reflected by the LF/HF ratio. (Author correspondence: Kurt.Kraeuchi@upkbs.ch)     

THE INFLUENCE OF CIRCADIAN PHASE AND PRIOR WAKE ON NEUROMUSCULAR FUNCTION

Previous forced desynchrony (FD) studies have shown that neurobehavioral function is affected by circadian phase and duration of prior wakefulness. There is some evidence that neuromuscular function may also be affected by circadian phase and prior wake, but these effects have not been systematically investigated. This study examined the effects of circadian phase and prior wake on two measures of neuromuscular function—postural balance (PB) and maximal grip strength (MGS)—using a 28-h FD protocol. Eleven male participants (mean?±?SD: 22.7?±?2.5 yr) lived in a sound-attenuated, light- and temperature-controlled time-isolation laboratory for 12 days. Following two training days and a baseline day, participants were scheduled to seven 28-h FD days, with the ratio between sleep opportunity and wake spans kept constant (i.e., 9.3?h sleep period and 18.7?h wake period). PB was measured during 1?min of quiet standing on a force platform. MGS of the dominant hand was measured using a dynamometer. These two measures were obtained every 2.5?h during wake. Core body temperature was continuously recorded with rectal thermistors to determine circadian phase. For both measures of neuromuscular function, individual data points were assigned a circadian phase and a level of prior wake. Data were analyzed by repeated-measures analysis of variance (ANOVA) with two within-subjects factors: circadian phase (six phases) and prior wake (seven levels). For MGS, there was a main effect of circadian phase, but no main effect of prior wake. For PB, there were no main effects of circadian phase or prior wake. There were no interactions between circadian phase and prior wake for MGS or PB. The significant effect of circadian phase on muscle strength is in agreement with previous reports in the literature. In terms of prior wake, both MGS and PB remained relatively stable across wake periods, indicating that neuromuscular function may be more robust than neurobehavioral function when the duration of wakefulness is within a normal range (i.e., 18.7?h). (Author correspondence: charli.sargent@unisa.edu.au)     

HABITUAL MODERATE ALCOHOL CONSUMPTION DESYNCHRONIZES CIRCADIAN PHYSIOLOGIC RHYTHMS AND AFFECTS REACTION-TIME PERFORMANCE

The authors studied longitudinally four healthy young adults to explore if habitual evening intake of a “moderate” amount of wine alters parameters, including period (τ) of circadian rhythms. Subjects, synchronized by diurnal activity from 07.30?h?±?60?min to 23.00?h?±?90?min and nocturnal rest, were studied during a continuous 22-day span: 11 days without alcohol (control) and 11 days with a glass (200?mL) of wine nightly at supper (alcohol). The amount of alcohol ingested with dinner ranged from 0.28 to 0.42?g/kg/24?h/participant and the estimated evening blood alcohol level ranged from 0.02 to 0.10?g/L/participant. Single reaction time (SRT; yellow light signal), three-choice reaction time (CRT) (red, green, and yellow signals) of both hands, related cumulated errors (c-errors), as well as oral temperature (OT) and grip strength (GS) were measured four to seven times/24?h. Time series were analyzed individually to quantify 24-h means (M), circadian τ (power spectra), and cosinor, and correlation, χ², and t tests were performed. The sleep-wake τ (actography) was 24?h in every subject for both conditions. With alcohol, all subjects showed an OT circadian τ shorter than the control one. The SRT circadian M was longer (poorer performance) with wine versus control in three subjects, while CRT was longer with wine versus control in only one subject. Correlation analyses also showed the detrimental effect of alcohol on the same variables. Number of days with <2 c-errors was predominant in control and decreased with alcohol, especially for SRT. The desynchronization of the 10 different documented rhythms was greater with alcohol with reference to control in two of the four studied subjects. This work shows that habitual "moderate" wine drinking at supper reduces the performance of subjects, increases the level of c-errors/24?h, especially for SRT, suggesting a “moderate” amount of alcohol has the potential to increase accident risk, and it can also desynchronize circadian time organization. (Author correspondence: bergarein@yahoo.fr)     

Towards a Characterization of the Locomotor Activity Rhythm of the Supralittoral Isopod Tylos europaeus

Freshly collected samples of Tylos europaeus from Korba beach (northeast of Tunisia) were housed in an environmental cabinet at controlled temperature (18°C?±?.5°C) and photoperiod. Locomotor activity was recorded under two photoperiodic regimens by infrared actography every 20?min by multichannel data loggers. One regimen simulated the natural light-dark cycle on the day of collection, whereas the second imposed a state of continuous darkness on all individuals. Under entraining conditions, the animals displayed rhythmic activity, in phase with the period of darkness, whereas in continuous darkness these isopods exhibited a strong endogenous rhythm with circadian and semidiurnal components at mean periods of τ (h:min)?=?25:09?±?01:02?h and τ?=?12:32?±?00:26?h, respectively. Under free-running conditions, this endogenous rhythm showed significant intraspecific variability. (Author correspondence: bohli.dhouha@gmail.com)     

Orcadian Rhythm of Serotonin Binding in Rat Brain—I. Effect of the Light-Dark Cycle

Moving rapidly from a supine to a standing posture is a common daily activity, yet a significant physiological challenge. Syncope can result from the development of initial orthostatic hypotension (IOH) involving a transient fall in systolic/diastolic blood pressure (BP) of >40/20?mm Hg within the first 15 s, and/or a delayed orthostatic hypotension (DOH) involving a fall in systolic/diastolic BP of >20/10?mm Hg within 15?min of posture change. Although epidemiological data indicate a heightened syncope risk in the morning, little is known about the diurnal variation in the IOH and DOH mechanisms associated with postural change. The authors hypothesized that the onset of IOH and DOH occurs sooner, and the associated cardiorespiratory and cerebrovascular changes are more pronounced, in the early morning. At 06:00 and 16:00?h, 17 normotensive volunteers, aged 26?±?1 yrs (mean?±?SE), completed a protocol involving supine rest, an upright stand, and a 60° head-up tilt (HUT) during which continuous beat-to-beat measurements of middle cerebral artery velocity (MCAv), mean arterial BP (MAP), heart rate, and end-tidal Pco₂ (P_ETco₂) were obtained. Mean MCAv was ～12% lower at baseline in the morning (p?≤?.01) and during the HUT (p?<?.01), despite a morning elevation in P_ETco₂ by ～2.2?mm Hg (p?=?.01). The decline in MAP during initial standing (morning vs. afternoon: 50%?±?4% vs. 49%?±?3%) and HUT (39%?±?3% vs. 38%?±?3%) did not vary with time-of-day (p?>?.30). In conclusion, although there is a marked reduction in MCAv in the morning, there is an absence of diurnal variation in the onset of and associated physiological responses associated with IOH and DOH. These responses, at least in this population, are unlikely contributors to the diurnal variation in orthostatic tolerance. (Author correspondence: N.C.Lewis@2004.ljmu.ac.uk)     

SLEEP PATTERNS IN HIGH SCHOOL AND UNIVERSITY STUDENTS: A LONGITUDINAL STUDY

We performed a longitudinal study to investigate whether changes in social zeitgebers and age alter sleep patterns in students during the transition from high school to university. Actimetry was performed on 24 high-school students (mean age?±?SD: 18.4?±?0.9 yrs; 12 females) for two weeks. Recordings were repeated in the same subjects 5 yrs later when they were university students. The sleep period duration and its center, the mid-sleep time, and total sleep time were estimated by actimetry. Actigraphic total sleep time was similar when in high school and at the university on school days (6.31?±?0.47 vs. 6.45?±?0.80?h, p?=?ns) and longer on leisure days by 1.10?±?1.10?h (p?<?0.0001 vs. school days) when in high school, but not at the university. Compared to the high school situation, the mid-sleep time was delayed when at the university on school days (03∶11?±?0.6 vs. 03∶55?±?0.7?h, p?<?0.0001), but not on leisure days. Individual mid-sleep times on school and leisure days when in high school were significantly correlated with the corresponding values 5 yrs later when at the university (r?=?0.58 and r?=?0.55, p?<?0.05, respectively). The large differences in total sleep time between school and leisure days when students attended high school and the delayed mid-sleep time on school days when students attended university are consistent with a circadian phase shift due to changes in class schedules, other zeitgebers, and lifestyle preferences. Age-related changes may also have occurred, although some individuality of the sleep pattern was maintained during the 5 yr study span. These findings have important implications for optimizing school and work schedules in students of different age and level of education. (Author correspondence: pneubloc@usz.uzh.ch)