Circadian Acrophase Research Articles

Validation of the Chinese version of the Munich Chronotype Questionnaire (MCTQHK) in Hong Kong Chinese youths

ABSTRACT Chronotype, referred to as an individual’s diurnal preference of timing for rest and activity, can be subjectively measured using the Munich Chronotype Questionnaire (MCTQ). However, the validity of MCTQ has yet to be tested in the youth population. In addition, it remains uncertain if MCTQ is a good measure of chronotype in individuals with insomnia. The current study aimed to validate the Chinese version of MCTQ (MCTQHK) in the youth population and to explore the utility of MCTQHK in individuals with insomnia. The original MCTQ was translated into Chinese language using the translation-back-translation method. Part one of this study included 988 youths who completed a battery of self-report questionnaires online consisting of the MCTQHK and the morningness-eveningness questionnaire (MEQ) for the measures of circadian preference, Insomnia Severity Index (ISI) to assess insomnia symptoms, and Patient Health Questionnaire (PHQ-9) to measure depressive symptoms. Test–retest reliability was examined in 442 participants at one-month follow-up. Of the overall sample, 69 participants were randomly drawn to complete the second part of the study, which included prospective 7-day actigraphy monitoring and a further subset (n = 40) additionally completed a laboratory-based assessment of dim-light melatonin onset (DLMO) as a circadian phase marker. A total of 659 participants with valid responses were finally included in the analyses of the data collected from part one of the study (female = 67.7%; mean age: 20.7 ± 2.02). Results showed that MCTQ parameters, namely the midpoint of sleep on free days (MSF), midpoint of sleep on workdays (MSW), and midpoint of sleep adjusted for sleep debt (MSFsc), were significantly correlated with MEQ score (r = −.514 to −.650, p < .01). Test–retest reliability for MCTQHK was good (intraclass correlation = 0.75 to 0.84). Later MSFsc was significantly associated with greater insomnia and depressive symptoms after controlling for age and sex. All MCTQ parameters showed significant correlations with actigraphy-based midpoint of sleep and circadian rhythm parameters, i.e., acrophase and L5 onset (r = .362 to .619, p < .01), as well as DLMO (r = .393 to .517, p < .05). The associations remained significant after controlling for age. MSFsc derived from MCTQ was significantly correlated with MEQ score in both the healthy sleepers and participants with insomnia (as defined by ISI > 14), r = −.600, p < .001 and r = −.543, p < .001, respectively. The present study demonstrated that MCTQHK is suitable for assessing chronotype with good reliability and validity in Chinese youths and supported the utility of MCTQHK in individuals with insomnia.

CosinoRmixedeffects: an R package for mixed-effects cosinor models

BackgroundWearable devices enable monitoring and measurement of physiological parameters over a 24-h period, and some of which exhibit circadian rhythm characteristics. However, the currently available R package cosinor could only analyze daily cross-sectional data and compare the parameters between groups with two levels. To evaluate longitudinal changes in the circadian patterns, we need to extend the model to a mixed-effect model framework, allowing for random effects and interaction between COSINOR parameters and time-varying covariates.ResultsWe developed the cosinoRmixedeffects R package for modelling longitudinal periodic data using mixed-effects cosinor models. The model allows for covariates and interactions with the non-linear parameters MESOR, amplitude, and acrophase. To facilitate ease of use, the package utilizes the syntax and functions of the widely used emmeans package to obtain estimated marginal means and contrasts. Estimation and hypothesis testing involving the non-linear circadian parameters are carried out using bootstrapping. We illustrate the package functionality by modelling daily measurements of heart rate variability (HRV) collected among health care workers over several months. Differences in circadian patterns of HRV between genders, BMI, and during infection with SARS-CoV2 are evaluated to illustrate how to perform hypothesis testing.ConclusioncosinoRmixedeffects package provides the model fitting, estimation and hypothesis testing for the mixed-effects COSINOR model, for the linear and non-linear circadian parameters MESOR, amplitude and acrophase. The model accommodates factors with any number of categories, as well as complex interactions with circadian parameters and categorical factors.

Locomotor activity rhythm of catfish Heteropneustes fossilis are prominently regulated by light-dark cues

It is interesting to explore, the circadian locomotor activity rhythm of dark adapted fishes. Therefore, it is aimed to investigate the circadian locomotor activity rhythm of catfish, Heteropneustes fossilis under different light regi-mens- light-dark condition LD 12:12, constant dark condition DD, constant light LL and dark-light condition DL 12:12 in both male and female. The study was conducted sequentially under LD 12: 12 (LON 0500 and LOFF 1700) and thereafter under the DD, LL and DL each for at least 10-12 consecutive days. The locomotor activity was monitored using Stanford Chronobiology Kit at a fixed period of 24 h. The three rhythm parameters obtained were Mesor (M, rhythm-adjusted 24-h average), amplitude (A) and acrophase (peak, Ø). All fish exhibited a statistically significant (p&lt;0.001) circadian rhythm in locomo-tor activity under all light regimens LD, DD, LL and DL. The circadian ampli-tude was significantly declined under constant DD and LL. A significant shift was displayed in the circadian acrophase in all fish under each photic re-gimes LD, DD, LL and DL. The effect of light condition on M, A and Ø was sig-nificant, while gender imposed no effect. Chi-square periodogram revealed τ &gt; 24 h in locomotor activity of most of the replicates under DD and LL. The respective study suggests that the endogenous circadian clocks in catfish H.fossilis are weakly expressed under constant conditions and requires light-dark LD or dark- light DL cues to generate/express the circadian rhythm in locomotor activity.

The Impact of Shift Work on Sleep, Alertness and Performance in Healthcare Workers

Shift work is associated with impaired alertness and performance due to sleep loss and circadian misalignment. This study examined sleep between shift types (day, evening, night), and alertness and performance during day and night shifts in 52 intensive care workers. Sleep and wake duration between shifts were evaluated using wrist actigraphs and diaries. Subjective sleepiness (Karolinska Sleepiness Scale, KSS) and Psychomotor Vigilance Test (PVT) performance were examined during day shift, and on the first and subsequent night shifts (3rd, 4th or 5th). Circadian phase was assessed using urinary 6-sulphatoxymelatonin rhythms. Sleep was most restricted between consecutive night shifts (5.74 ± 1.30 h), consecutive day shifts (5.83 ± 0.92 h) and between evening and day shifts (5.20 ± 0.90 h). KSS and PVT mean reaction times were higher at the end of the first and subsequent night shift compared to day shift, with KSS highest at the end of the first night. On nights, working during the circadian acrophase of the urinary melatonin rhythm led to poorer outcomes on the KSS and PVT. In rotating shift workers, early day shifts can be associated with similar sleep restriction to night shifts, particularly when scheduled immediately following an evening shift. Alertness and performance remain most impaired during night shifts given the lack of circadian adaptation to night work. Although healthcare workers perceive themselves to be less alert on the first night shift compared to subsequent night shifts, objective performance is equally impaired on subsequent nights.

Effect of gender, age, diet and smoking status on the circadian rhythm of ascorbic acid (vitamin C) of healthy Indians

Background/ObjectivesTo determine effects of gender, age, diet, and smoking status on circadian rhythm characteristics of ascorbic acid (vitamin C). Subjects/MethodsAscorbic acid was measured spectrophotometrically in serum collected from 162 healthy volunteers (103 males and 59 females; 7–75 years) every 6h for 24h (4 samples). Data were analyzed by single and population mean cosinor. Effects of gender, age, diet (vegetarian vs. omnivore), and smoking status on the rhythm-adjusted mean (MESOR) and circadian amplitude were examined by multiple analysis of variance. ResultsA circadian rhythm is documented with statistical significance by population mean cosinor. In addition to effects of gender and age, the MESOR is affected by diet and smoking status. The circadian amplitude changes nonlinearly as a function of age. The circadian acrophase advances with increasing age. ConclusionThe present observations confirm a definite circadian rhythm in ascorbic acid concentrations with significant effects of age, diet and smoking status in clinical health. Mapping the circadian rhythm of serum ascorbic acid in health can help explore its role in different pathophysiological conditions as pre-disease conditions may be characterized by alterations in the circadian amplitude and/or phase before there is a change in mean value.

Circadian time structure of circulating plasma lipid peroxides, antioxidant enzymes and other small molecules in peptic ulcers

BackgroundThe circadian rhythm, as part of a broad time structure (chronome) of lipid peroxides and antioxidant defense mechanisms may relate to prevention, efficacy and management of preventive and curative chronotherapy. MethodsFifty newly diagnosed patients with peptic ulcers, 30–45years of age, and 60 age-matched clinically healthy volunteers were synchronized for one week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was served around 08:30, lunch around 13:30 and dinner around 20:30. Drugs known to affect the free-radical systems were not taken. Blood samples were collected at 6-hour intervals for 24h under standardized, presumably 24-hour synchronized conditions. Plasma lipid peroxides, in the form of malondialdehyde (MDA), blood superoxide dismutase (SOD), glutathione peroxide (GPx), glutathione reductase (GR), catalase (CAT) activities, and serum total protein, albumin, ascorbic acid, total serum cholesterol, and HDL-cholesterol concentrations were determined. ResultsBy population-mean cosinor analysis, a marked circadian variation was demonstrated for all variables in healthy subjects and in ulcer patients (p<0.001). As compared to controls, patients had a lower MESOR of MDA, SOD, GPx, GR, ascorbic acid, and HDL-C. They also had smaller circadian amplitude of SOD, CAT, GPx, GR, ascorbic acid, T-C, and HDL-C, but larger circadian amplitude of MDA and albumin. As compared to healthy subjects, the circadian acrophase of ulcer patients occurred later for MDA and GR and earlier for GPx. ConclusionMapping circadian rhythms, important chronome components that include trends with age and extra-circadian components characterizing antioxidants and pro-oxidants, is needed for exploring their putative role as markers in the treatment and management of peptic ulcers.

Circadian rhythm of serum 25 (OH) vitamin D, calcium and phosphorus levels in the treatment and management of type-2 diabetic patients.

The circadian time structure of serum 25 (OH) vitamin D (25-OHD), calcium (Ca) and phosphorus (P) may prove to be helpful in prevention, efficacy and management of diabetes mellitus. Ten newly diagnosed patients with type-2 diabetes mellitus (6 men and 4 women), 30-65 years of age, and 10 age-matched clinically healthy volunteers (7 men and 3 women) were synchronized for one week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was served around 08:00, lunch around 13:30 and dinner around 20:00. Drugs/nutraceuticals known to affect the vitamin D-calcium metabolism and status were not taken. Blood samples were collected at 6-h intervals for 24 h under standardized, 24-h synchronized conditions. Serum 25-OHD, Ca, P, Ca-P product and Ca-P ratio were determined. A marked circadian variation was demonstrated for 25-OHD in healthy volunteers (p = 0.030) and of borderline statistical significance in the diabetic patients (p = 0.083) by population-mean cosinor analysis. Similarly, healthy volunteers showed borderline significance for serum Ca, P and Ca-P ratio. The circadian acrophase of Ca occurred later in the patients as compared to healthy controls. Mapping the circadian rhythm (an important component of the broader time structure or chronome, which includes a.o., trends with age and extra-circadian components) of vitamin D and calcium is needed for exploring their role as markers in the treatment and management of diabetic patients.

The effects of a split sleep–wake schedule on neurobehavioural performance and predictions of performance under conditions of forced desynchrony

Extended wakefulness, sleep loss, and circadian misalignment are factors associated with an increased accident risk in shiftwork. Splitting shifts into multiple shorter periods per day may mitigate these risks by alleviating prior wake. However, the effect of splitting the sleep–wake schedule on the homeostatic and circadian contributions to neurobehavioural performance and subjective assessments of one’s ability to perform are not known. Twenty-nine male participants lived in a time isolation laboratory for 13 d, assigned to one of two 28-h forced desynchrony (FD) schedules. Depending on the assigned schedule, participants were provided the same total time in bed (TIB) each FD cycle, either consolidated into a single period (9.33 h TIB) or split into two equal halves (2 × 4.67 h TIB). Neurobehavioural performance was regularly assessed with a psychomotor vigilance task (PVT) and subjectively-assessed ability was measured with a prediction of performance on a visual analogue scale. Polysomnography was used to assess sleep, and core body temperature was recorded to assess circadian phase. On average, participants obtained the same amount of sleep in both schedules, but those in the split schedule obtained more slow wave sleep (SWS) on FD days. Mixed-effects ANOVAs indicated no overall difference between the standard and split schedules in neurobehavioural performance or predictions of performance. Main effects of circadian phase and prior wake were present for both schedules, such that performance and subjective ratings of ability were best around the circadian acrophase, worst around the nadir, and declined with increasing prior wake. There was a schedule by circadian phase interaction for all neurobehavioural performance metrics such that performance was better in the split schedule than the standard schedule around the nadir. There was no such interaction for predictions of performance. Performance during the standard schedule was significantly better than the split schedule at 2 h of prior wake, but declined at a steeper rate such that the schedules converged by 4.5–7 h of prior wake. Overall, the results indicate that when the total opportunity for sleep per day is satisfactory, a split sleep–wake schedule is not detrimental to sleep or performance. Indeed, though not reflected in subjective assessments of performance capacity, splitting the schedule may be of some benefit, given its reduction of neurobehavioural impairment at night and its association with increased SWS. Therefore, for some industries that require operations to be sustained around the clock, implementing a split work–rest schedule may be of assistance.

Actigraphy in patients with treatment-resistant depression undergoing electroconvulsive therapy

Depressive disorder is frequently accompanied by changes in psychomotor activity and disturbances of the sleep–wake cycle. The chronobiological effects of electroconvulsive therapy (ECT) in patients with treatment-resistant depression (TRD) are largely unknown. The objective of the current study was to measure the influence of ECT on patients' activity and sleep. 15 patients with unipolar TRD were treated with ECT. Activity levels were measured with wrist actigraphy before and after ECT. Remission rate (score on the 17-item Hamilton Depression Rating Scale lower than 8 points) was 40.0%. Remitters had increases of 56.0% on light activity, 49.8% on total activity, and 70.2% on circadian amplitude, while there was no significant change of these variables in subjects who did not experience remission. The circadian acrophase and actigraphic sleep-parameters were not significantly affected by treatment.

Thoracic surface temperature rhythms as circadian biomarkers for cancer chronotherapy

The disruption of the temperature circadian rhythm has been associated with cancer progression, while its amplification resulted in cancer inhibition in experimental tumor models. The current study investigated the relevance of skin surface temperature rhythms as biomarkers of the Circadian Timing System (CTS) in order to optimize chronotherapy timing in individual cancer patients. Baseline skin surface temperature at four sites and wrist accelerations were measured every minute for 4 days in 16 patients with metastatic gastro-intestinal cancer before chronotherapy administration. Temperature and rest-activity were recorded, respectively, with wireless skin surface temperature patches (Respironics, Phillips) and an actigraph (Ambulatory Monitoring). Both variables were further monitored in 10 of these patients during and after a 4-day course of a fixed chronotherapy protocol. Collected at baseline, during and after therapy longitudinal data sets were processed using Fast Fourier Transform Cosinor and Linear Discriminant Analyses methods. A circadian rhythm was statistically validated with a period of 24 h (p < 0.05) for 49/61 temperature time series (80.3%), and 15/16 rest-activity patterns (93.7%) at baseline. However, individual circadian amplitudes varied from 0.04 °C to 2.86 °C for skin surface temperature (median, 0.72 °C), and from 16.6 to 146.1 acc/min for rest-activity (median, 88.9 acc/min). Thirty-nine pairs of baseline temperature and rest-activity time series (75%) were correlated (r > |0.7|; p < 0.05). Individual circadian acrophases at baseline were scattered from 15:18 to 6:05 for skin surface temperature, and from 12:19 to 15:18 for rest-activity, with respective median values of 01:10 (25–75% quartiles, 22:35–3:07) and 14:12 (13:14–14:31). The circadian patterns in skin surface temperature and rest-activity persisted or were amplified during and after fixed chronotherapy delivery for 5/10 patients. In contrast, transient or sustained disruption of these biomarkers was found for the five other patients, as indicated by the lack of any statistically significant dominant period in the circadian range. No consistent correlation (r < |0.7|, p ≥ 0.05) was found between paired rest-activity and temperature time series during fixed chronotherapy delivery. In conclusion, large inter-patient differences in circadian amplitudes and acrophases of skin surface temperature were demonstrated for the first time in cancer patients, despite rather similar rest-activity acrophases. The patient-dependent coupling between both CTS biomarkers, and its possible alteration on a fixed chronotherapy protocol, support the concept of personalized cancer chronotherapy.

Differences in circadian time structure of diastolic blood pressure between diabetes mellitus and essential hypertension

BackgroundAbnormal circadian blood pressure patterns have been associated with cardiovascular disease in diabetes mellitus. We have described that the acrophase of diastolic blood pressure (DBP) registered in type 1 diabetes (T1D) patients was significantly earlier than normal and DBP ecphasia was more pronounced in patients with lower heart rate variability during deep breathing. The aim of this study was to compare the circadian rhythm characteristics of BP among different groups: normotensive (NT) control subjects, patients affected by T1D and type 2 diabetes (T2D), and patients with essential hypertension (HT).FindingsWe retrospectively evaluated ambulatory blood pressure monitoring records in 30 NT, 20 T1D, 20 T2D, 20 HT whose fasting plasma glucose and HbA1c were contemporaneously measured. The four groups were well-matched regarding age, gender, and BMI.Systolic blood pressure (SBP) and DBP midline-estimating statistic of rhythm were higher in T1D, T2D, and HT groups. DBP ecphasia was present only in the diabetic individuals: the acrophase of DBP occurred four hours earlier than normal in T1D group, whereas two hours earlier in T2D group. In a multiple regression analysis, only HbA1c and SBP acrophase were statistically significant correlates of DBP acrophase.ConclusionsPeople with diabetes mellitus, both type 1 and type 2, have their circadian acrophase of DBP occurring 2–4 hours earlier than normotensive and hypertensive subjects. Altered circadian timing of DBP, potential trigger of cardiovascular events, seems to be a distinguishing feature of diabetes mellitus and correlates with the previous 2–3 months of glycaemic control.

Effect of induced Dalton's lymphoma on circadian locomotor activity rhythm of adult male mice

Dalton's lymphoma (DL) is a spontaneous and highly invasive T-cell lymphoma that develops as an ascitic tumor in murines. DL was induced by serial implantation of live ascite cells in laboratory-acclimated age-matched male AKR mice. The effects of DL on the locomotor activity rhythm were studied under 12:12 h light:dark (LD) cycle. A significant decrease in the total and peak wheel-running activity was seen after the induction of DL, in comparison with the vehicle-injected control group. Durations of activity and rest were altered in DL mice, with a sharp daily increase in the duration of rest in the DL group. Circadian time period and acrophase of the rhythm remained similar in both control and DL mice. The mean estimate of statistic of rhythmicity (MESOR) and the amplitude of the locomotor activity rhythm were significantly lesser in post-DL-induced mice. A reduction in the span of the M1 and M2 motor cortex regions in DL mice and anatomical changes in the dentate gyrus were also seen. Thus, the effects of DL on the circadian clock seem restricted and mouse can still synchronize to an LD cycle. Impact of DL extends to motor cortices and may be the cause of the dampening of the amplitude of the rest-activity rhythm.

Circadian blood pressure and heart rate characteristics in haemorrhagic vs ischaemic stroke in Chinese people

To compare the circadian variation of blood pressure (BP) between patients with intra-cerebral haemorrhage (ICH) and with cerebral infarction (CI), around-the-clock BP measurements were obtained from 89 hypertensive patients with ICH, from 63 patients with CI and from 16 normotensive volunteers. The single and population-mean cosinor yielded individual and group estimates of the MESOR (Midline Estimating Statistic Of Rhythm, a rhythm-adjusted mean value), circadian double amplitude and acrophase (measures of extent and timing of predictable daily change). Comparison shows that without any difference in BP MESOR, the circadian amplitude of systolic (S) BP was larger in ICH than CI patients (P<0.001), and both groups differed from the healthy volunteers in BP MESOR and pulse pressure (P<0.001) and in the circadian amplitude of SBP (P<0.005). The smaller population circadian amplitude of diastolic (D) BP of the ICH group (P=0.042) is likely related to a larger scatter of individual circadian acrophases in this group as compared with that in the other two groups, an inference supported by a smaller day-night ratio of DBP for ICH vs CI patients (P=0.007). Heart rate (HR) variability, gauged by the standard deviation (SD), was decreased in both patient groups as compared with that in healthy controls, more so among ICH than CI patients (P=0.025). Thus, patients with ICH had a higher incidence of abnormal circadian characteristics of BP than patients with CI, the major differences relating to a larger circadian amplitude of SBP, a smaller HR-SD, and a larger incidence of odd circadian acrophases of DBP.

Clock Gene Expression in the Murine Gastrointestinal Tract: Endogenous Rhythmicity and Effects of a Feeding Regimen

Based on observations that the gastrointestinal tract is subject to various 24-hour rhythmic processes, it is conceivable that some of these rhythms are under circadian clock gene control. We hypothesized that clock genes are present in the gastrointestinal tract and that they are part of a functional molecular clock that coordinates rhythmic physiologic functions. The effects of timed feeding and vagotomy on temporal clock gene expression (clock, bmal1, per1-3, cry1-2) in the gastrointestinal tract and suprachiasmatic nucleus (bmal, per2) of C57BL/6J mice were examined using real-time polymerase chain reaction and Western blotting (BMAL, PER2). Colonic clock gene localization was examined using immunohistochemistry (BMAL, PER1-2). Clock immunoreactivity was observed in the myenteric plexus and epithelial crypt cells. Clock genes were expressed rhythmically throughout the gastrointestinal tract. Timed feeding shifted clock gene expression at the RNA and protein level but did not shift clock gene expression in the central clock. Vagotomy did not alter gastric clock gene expression compared with sham-treated controls. The murine gastrointestinal tract contains functional clock genes, which are molecular core components of the circadian clock. Daytime feeding in nocturnal rodents is a strong synchronizer of gastrointestinal clock genes. This synchronization occurs independently of the central clock. Gastric clock gene expression is not mediated through the vagal nerve. The presence of clock genes in the myenteric plexus and epithelial cells suggests a role for clock genes in circadian coordination of gastrointestinal functions such as motility, cell proliferation, and migration.

Pathophysiology of hypercortisolism in depression

The mechanisms mediating hypercortisolemia in depression remain controversial. Adopting the biomarker strategy, we studied adrenocorticotropin (ACTH) and cortisol dynamics in hypercortisolemic and non-hypercortisolemic depressed in-patients, and in normal volunteers. Deconvolution analysis of 24-h pulsatile secretion, approximate entropy (ApEn) estimation of secretory regularity, cross-ApEn quantitation of forward and reverse ACTH-cortisol synchrony, and cosine regression of 24-h rhythmicity. Hypercortisolemia was strongly associated with melancholic and psychotic depressive subtypes. Hypercortisolemic patients had elevated ACTH and cortisol secretion, mediated chiefly by increased burst masses. Basal ACTH secretion was increased, ACTH half-life was reduced, and mean 24-h ACTH concentration was normal. Cortisol secretion was increased in a highly irregular pattern (high ApEn), with high ACTH --> cortisol cross-ApEn (impaired feedforward coupling). Cortisol-mediated feedback on the secretory pattern of ACTH was normal. Hypercortisolemic depressed patients had normal programming of the central hypothalamo-pituitary-adrenal (HPA) axis pulse generator: ACTH pulse frequency, cortisol pulse frequency, circadian acrophases, and ApEn of ACTH secretion were normal. Responsiveness of the adrenal cortex to endogenous ACTH was normal. Non-hypercortisolemic patients resembled hypercortisolemic patients on ACTH regulatory parameters but had low total cortisol secretion. Increased ACTH secretion occurs in depressed in-patients regardless of cortisolemic status, confirming central HPA axis overdrive in severe depression. Depressive hypercortisolemia results from an additional change in the adrenal cortex that causes ACTH-independent, disorderly basal cortisol release, a sign of physiological stress in melancholic/psychotic depression.

Effect of Time of Day on Aerobic Contribution to the 30‐s Wingate Test Performance

The purpose of this study was to evaluate the effects of time of day on aerobic contribution during high‐intensity exercise. A group of 11 male physical education students performed a Wingate test against a resistance of 0.087 kg · kg−1 body mass. Two different times of day were chosen, corresponding to the minimum (06:00 h) and the maximum (18:00 h) levels of power. Oxygen uptake (V˙O2) was recorded breath by breath during the test (30 sec). Blood lactate concentrations were measured at rest, just after the Wingate test, and again 5 min later. Oral temperature was measured before each test and on six separate occasions at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00 h. A significant circadian rhythm was found in body temperature with a circadian acrophase at 18:16±00:25 h as determined by cosinor analysis. Peak power (Ppeak), mean power (Pmean), total work done, and V˙O2 increased significantly from morning to afternoon during the Wingate Test. As a consequence, aerobic contribution recorded during the test increased from morning to afternoon. However, no difference in blood lactate concentrations was observed from morning to afternoon. Furthermore, power decrease was greater in the morning than afternoon. Altogether, these results indicate that the time‐of‐day effect on performances during the Wingate test is mainly due to better aerobic participation in energy production during the test in the afternoon than in the morning.

The Circadian Body Temperature Rhythm in the Elderly: Effect of Single Daily Melatonin Dosing

The present study is part of a more extensive investigation dedicated to the study and treatment of age‐dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self‐chosen sleep‐wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen™) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age‐dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra‐ and inter‐individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38±0.19°C vs. 36.17±0.21°C) and circadian amplitude (0.33±0.01°C vs. 0.26±0.01°C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19±1.66 vs. 16.93±3.08 h). However, the inter‐individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter‐daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1°C and the amplitude increased to 0.34±0.01°C, a similar value to that found in young adults. This was probably due to the increase of the inter‐daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter‐individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age‐dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep‐improving effects.

Chronomics: circadian lead of extrapineal vs. pineal melatonin rhythms with an infradian hypothalamic exploration

A circadian rhythm is documented for plasma, pineal, and hypothalamic melatonin of male and female rats kept on staggered lighting regimens. Log[_10]-transformation of the data usually normalizes, when need be, the distribution of residuals from the 24-hour cosine curve fits. A tentative circadian acrophase chart is presented that shows a lead in circadian acrophase of duodenal over pineal melatonin. The use of antiphasic lighting regimens facilitates circadian studies that can be carried out for several days, thereby allowing the assessment of infradian components such as a circasemiseptan variation in hypothalamic melatonin documented herein. The results are qualified by the presence of a second extremum of a double magnetic storm at the start of mapping.

Changes in circadian LH-secretion patterns and annual gonadal cycles in the male European starling (Sturnus vulgaris)

An analysis of the circadian and circannual patterns of luteinizing hormone (LH) secretion in male European starlings (Sturnus vulgaris) held in outdoor aviaries is presented. On the basis of six daily time points, eight calendar dates, and seven individuals per sampling unit, we present a mathematical model developed to compare the two temporal patterns of secretion, the circadian and the circannual one. The superposition of four orthonormal trigonometric base functions, plus a constant, is used to examine the daily fluctuations. The contribution of the second harmonic was not the same at each calendar date. From the subsequent regression functions, hourly estimates of LH concentration were calculated and used to construct circannual cubic splines and an LH(t,T) function over the whole year. The model features indicate strong circannual and circadian components in the data. In addition, there appear to be two daily time regions of LH secretion: morning and afternoon. In particular, the afternoon maxima occur during photorefractoriness and early gonadal development; the morning maxima at the onset of photoinduction and late gonadal development. At the peak of gonadal activity (end of April), the highest LH levels occur during the photic input phase. It appears, then, that the circadian acrophase of LH secretion in male starlings fluctuates over the annual cycle of gonadal activity in a highly predictive and biologically interpretable manner.

Acute administration of the novel serotonin and noradrenaline reuptake inhibitor, S33005, markedly modifies sleep–wake cycle architecture in the rat

The interrelationship between depressive states and sleep-wake cycle architecture is characterised by a decreased latency to the first paradoxical sleep (PS) episode, together with an enhancement of PS during the first part of the night. Conversely, slow-wave sleep (SWS) is decreased and intermittent awakenings increased. Notably, antidepressant treatment is generally associated with a diminution of PS. In light of these observations, we examined the influence of acute administration of the novel mixed serotonin-noradrenaline reuptake blocker, (-)1-(1-dimethylaminomethyl 5-methoxybenzocyclobutan-1-yl)-cyclohexanol HCl (S33005), upon sleep-wake architecture in rats. Animals were injected with vehicle or incremental doses of S33005 at the onset of either the dark or light periods. Digitised polygraphic recordings were performed, and changes evoked by S33005 were determined over 24-h recording periods, i.e., number and duration of sleep-wake episodes, latencies to PS and SWS, power band spectra of the electroencephalogram (EEG) and circadian changes. At 0.04 mg/kg, S33005 was inactive, whereas at 0.63 mg/kg, it modestly increased PS latencies and diminished PS duration during the light period. At 10 mg/kg, S33005 reduced markedly PS duration for about 4-h when injected prior to both light and dark periods. Latency to PS was prolonged, and the circadian acrophase was delayed. These effects are in keeping with previous studies of monoamine reuptake inhibitors, but, notably, SWS duration was increased when S33005 was injected at the onset of the light phase (+4%). These changes occurred without marked modifications in circadian rhythmicity or EEG spectral band power. Finally, even at the highest dose of S33005, only a limited rebound of SWS (+5%) and PS (+10%) was apparent. Amongst antidepressant to date examined, this is an original profile of influence upon sleep patterns. These results demonstrate a pattern of influence of S33005 upon sleep-wake architecture in rats which is globally consistent with antidepressant properties, but with a distinctive enhancement of restorative slow-wave sleep.