Data-driven modelling approach to circadian temperature rhythm profiles in free-living conditions

The individual variation in the circadian rhythms at the physiological level is not well understood. Albeit self-reported circadian preference profiles have been consolidated, their premises are grounded on human experience, not on physiology. We used data-driven, unsupervised time series modelling to characterize distinct profiles of the circadian rhythm measured from skin surface temperature in free-living conditions. We demonstrate the existence of three distinct clusters of individuals which differed in their circadian temperature profiles. The cluster with the highest temperature amplitude and the lowest midline estimating statistic of rhythm, or rhythm-adjusted mean, had the most regular and early-timed sleep–wake rhythm, and was the least probable for those with a concurrent delayed sleep phase, or eveningness chronotype. While the clusters associated with the observed sleep and circadian preference patterns, the entirely unsupervised modelling of physiological data provides a novel basis for modelling and understanding the human circadian functions in free-living conditions.

Characterizing the modern light environment and its influence on circadian rhythms

Humans have largely supplanted natural light cycles with a variety of electric light sources and schedules misaligned with day-night cycles. Circadian disruption has been linked to a number of disease processes, but the extent of circadian disruption among the population is unknown. In this study, we measured light exposure and wrist temperature among residents of an urban area during each of the four seasons, as well as light illuminance in nearby outdoor locations. Daily light exposure was significantly lower for individuals, compared to outdoor light sensors, across all four seasons. There was also little seasonal variation in the realized photoperiod experienced by individuals, with the only significant difference occurring between winter and summer. We tested the hypothesis that differential light exposure impacts circadian phase timing, detected via the wrist temperature rhythm. To determine the influence of light exposure on circadian rhythms, we modelled the impact of morning and night-time light exposure on the timing of the maximum wrist temperature. We found that morning and night-time light exposure had significant but opposing impacts on maximum wrist temperature timing. Our results demonstrate that, within the range of exposure seen in everyday life, night-time light can delay the onset of the maximum wrist temperature, while morning light can lead to earlier onset. Our results demonstrate that humans are minimizing natural seasonal differences in light exposure, and that circadian shifts and disruptions may be a more regular occurrence in the general population than is currently recognized.

Negative Energy Balance Enhances Ultradian Rhythmicity in Spring-Programmed Voles

Voles are small herbivorous rodents that can display both circadian activity rhythms (~24-h periodicity) and ultradian activity rhythms (~1- to 6-h periodicity). Ultradian rhythms are observed on an individual level, but also in synchronized populations. Ultradian rhythm period has been suggested to be influenced by energy balance, but the underlying mechanisms of ultradian rhythmicity are poorly understood. We manipulated energy balance by implementing the “work-for-food” paradigm, in which small rodents are exposed to increasing levels of food scarcity at different ambient temperatures in the laboratory. Photoperiodical spring-programmed voles on high workload changed their nocturnal circadian activity and body temperature rhythm to ultradian patterns, indicating that a negative energy balance induces ultradian rhythmicity. This interpretation was confirmed by the observation that ultradian patterns arose earlier at low temperatures. Interestingly, a positive relationship between ultradian period length and workload was observed in tundra voles. Spectral analysis revealed that the power of ultradian rhythmicity increased at high workload, whereas the circadian component of running wheel activity decreased. This study shows that the balance between circadian and ultradian rhythmicity is determined by energy balance, confirming flexible circadian and ultradian rhythms in females and males of 2 different vole species: the common vole ( Microtus arvalis) and the tundra vole ( Microtus oeconomus).

Peripheral body temperature rhythm is associated with suicide risk in major depressive disorder: a case-control study

BackgroundPatients with major depressive disorder (MDD) may have an abnormal peripheral body temperature rhythm, but its relationship with suicidal risk and the response to treatment with antidepressants remain unknown.AimsThis study aimed to investigate the feature of peripheral body temperature in patients with MDD and its relationship with suicide risk before and after treatment with antidepressants.MethodsThis is a prospective case-control study. Patients diagnosed as MDD were enrolled into MDD group. Healthy subjects who matched in terms of gender, age and body mass index were enrolled into normal control (NC) group. The 24-hour peripheral body temperatures were monitored by TM’ Holter the next day after assessment. Patients with MDD were re-assessed after a 2-week treatment with antidepressants. All temperature data were fitted into cosine curves by Python.ResultThere were 41 patients with MDD, and 21 NC participants enrolled and completed the baseline assessments before the treatment. Patients with MDD were further divided into subgroup of with suicide risk or without suicide risk. In patients with MDD, the mesor of peripheral body temperature rhythm was higher in both patients with (36.17 (0.30)) and without suicide risk (36.22 (0.27)) than the mesor in NC participants before treatment (35.84 (0.38), Z=11.82, p=0.003, Kruskal-Wallis test). The phase-delay of temperature before treatment was greater in patients with MDD with suicidal risk (4.71 (1.68)) in comparison with those without suicidal risk (3.05 (2.19)) and NC participants (3.19 (1.82), Z=9.68, p=0.008, Kruskal-Wallis test). Moreover, phase-delay of temperature was associated with suicide risk in patients with MDD before treatment (OR=1.046, 95% CI: 1.009 to 1.085, p=0.015, unadjusted; OR=1.080, 95% CI: 1.020 to 1.144, p=0.009, adjusted by age and sex).ConclusionPatients with MDD might have abnormal peripheral body temperature. The abnormal phase-delay of peripheral body temperature may indicate suicide risk in patients with MDD, depending on validation in large-scale cohorts.

Circadian Patterns of Patients with Type 2 Diabetes and Obstructive Sleep Apnea

Sleep apnea, a condition that modifies sleep and circadian rhythms, is highly prevalent in patients with diabetes. However, it is not known if there is an association between sleep apnea, circadian alterations and glycemic regulation in this type of patient. Here, a polysomnographic study was carried out on 21 women and 25 men (mean age = 64.3 ± 1.46 years) with diagnoses of type 2 diabetes to detect the presence of sleep apnea. Moreover, patients wore an actigraph and a temperature sensor on the wrist for one week, to study the manifestation of the circadian rhythms. The correlations of circadian and polysomnographic variables with the severity of apnea, measured by the apnea-hypopnea index, and with glycemic dysregulation, measured by the percentage of glycated hemoglobin, were analyzed. The mean apnea-hypoapnea index of all the participants was 39.6 ± 4.3. Apnea-hypoapnea index correlated with % N1, negatively with % N3, and also the stability of the active circadian rhythm. However, no significant correlation was found between the apnea-hypopnea index and wrist temperature rhythm and glycated hemoglobin. Glycated hemoglobin levels were negatively associated with the percentage of variance explained by the wrist temperature circadian rhythm (calculated via 24 and 12 h rhythms). This association was independent of body mass index and was strongest in patients with severe apnea. In conclusion, patients with diabetes showed altered circadian rhythms associated with a poor glycemic control and this association could partially be related to the coexistence of sleep apnea.

Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma

Parameters of 24-h rhythm in intraocular pressure (IOP) were assessed in patients with stable or advanced primary open-angle glaucoma (S-POAG/A-POAG) and referenced to the phase of “marker” circadian temperature rhythm of each patient. Body temperature and IOP were measured over a 72-h span in 115 participants (65 S-POAG and 50 A-POAG). Retinal Ganglion Cell (RGC) damage was assessed by high-definition optical coherence tomography. The 24-h IOP rhythm in A-POAG patients peaked during the night, opposite to the daytime phase position in S-POAG patients (p < 0.0001). The 24-h IOP phase correlated with RGC loss (p < 0.0001). The internal phase shift between IOP and body temperature gradually increased with POAG progression (p < 0.001). Angiotensin converting enzyme Alu-repeat deletion/insertion (ACE I/D) emerged as a candidate gene polymorphism, which may play a role in the alteration of the circadian IOP variability in advanced glaucoma. To conclude, a reliable estimation of the 24-h rhythm in IOP requires the degree of RGC damage to be assessed. In advanced POAG, the 24-h phase of IOP tended to occur during the night and correlated with RGC loss, being progressively delayed relative to the phase of temperature.

Circadian regulation of breath alcohol concentration

Study objectives The role of the circadian clock in regulating blood/breath alcohol levels after consuming alcohol is uncertain. Our goal was to evaluate the degree to which the circadian system regulates breath alcohol concentration (BrAC) pharmacokinetic parameters. Methods Twenty healthy adults aged 21-30 y took part in a 4-d laboratory study. A 40-h constant routine procedure was used to assess circadian rhythms. Every 4 h, participants were given a fixed oral dose of alcohol with breathalyzer measurements taken every 5 min to construct BrAC curves. Sinusoidal models were used to test for circadian variation of the peak BrAC, the time to reach peak BrAC, the absorption rate, the elimination rate, and the time for BrAC to return to zero after alcohol was ingested. Results A significant circadian rhythm was detected for group-averaged peak BrAC values and the time for BrAC to return to zero, but not other BrAC variables. Peak BrAC values were lowest in the evening near the peak of the core body temperature rhythm and nadir of the salivary cortisol rhythm. Peak BrAC values increased during the night and reached their highest levels in the morning and afternoon. The time needed for BrAC to return to zero was also longest in the late morning and afternoon. Conclusion The circadian system modulates some BrAC pharmacokinetic parameters. In normally entrained individuals, taking the same oral dose of alcohol at different times of day can result in different BrAC responses. These findings have potential implications for alcohol-related accidents and alcohol toxicity.

Basic concepts and unique features of human circadian rhythms: implications for human health

Most physiological functions and behaviors exhibit a robust approximately 24-hour rhythmicity (circadian rhythm) in the real world. These rhythms persist under constant conditions, but the period is slightly longer than 24 hours, suggesting that circadian rhythms are endogenously driven by an internal, self-sustained oscillator. In mammals, including humans, the central circadian pacemaker is located in the hypothalamic suprachiasmatic nucleus. The primary zeitgeber for this pacemaker is bright sunlight, but nonphotic time cues also affect circadian rhythms. The human circadian system uniquely exhibits spontaneous internal desynchronization between the sleep-wake cycle and core body temperature rhythm under constant conditions and partial entrainment of the sleep-wake cycle in response to nonphotic time cues. Experimental and clinical studies of human circadian rhythms must take into account these unique features. This review covers the basic concepts and unique features of the human circadian system, the mechanisms underlying phase adjustment of the circadian rhythms by light and nonphotic time cues (eg, physical exercise), and the effects of eating behavior (eg, chewing frequency) on the circadian rhythm of glucose metabolism.