Clocks & Sleep, Volume 4, Issue 1 (March 2022) – 18 articles

Previous investigations in humans and rodent animal models have assessed the interplay of sleep in the circadian system’s phase responses to nighttime light exposure. The resulting data have been mixed, but generally support a modulatory role for sleep in circadian photic resetting (not an absolute requirement). Drosophila have been historically used to provide important insights in the sleep and circadian sciences. However, no experiments to date have evaluated how immediate sleep need or recent sleep history affects their pacemaker’s phase readjustments to light. We did so in the current study by (1) forcing separate groups of animals to stay awake for 1 or 4 h after they were shown a broadspectrum pulse (15 min during the first half of the night, 950 lux), or (2) placing them on a restricted sleep schedule for a week before light presentation without any subsequent sleep disruption. Forced sleep restriction, whether acute or chronic, did not alter the size of light-induced phase shifts. These data are consistent with observations made in other diurnal animals and raise the possibility, more broadly, that phototherapies applied during sleep—such as may be necessary during the winter months—may still be efficacious in individuals experiencing sleep-continuity problems such as insomnia. Full article

Circadian rhythms are self-sustained oscillators with a period of 24 h that is based on the output of transcriptional and post-translational feedback loops. Phosphorylation is considered one of the most important post-translational modifications affecting rhythmicity from cyanobacteria to mammals. For example, the lack of cyclin-dependent kinase 5 (CDK5) shortened the period length of the circadian oscillator in the Suprachiasmatic Nuclei (SCN) of mice via the destabilization of the PERIOD 2 (PER2) protein. Here, we show that CDK5 kinase activity and its interaction with clock components, including PER2 and CLOCK, varied over time in mouse embryonic fibroblast cells. Furthermore, the deletion of Cdk5 from cells resulted in a prolonged period and shifted the transcription of clock-controlled genes by about 2 to 4 h with a simple delay of chromatin binding of ARNTL (BMAL1) CLOCK. Taken together, our data indicate that CDK5 is critically involved in regulating the circadian clock in vitro at the molecular level. Full article

Several studies have reported that the COVID-19 pandemic has had deleterious effects on sleep quality and mood, but the mechanisms underlying these effects are not clearly understood. Recently, it has been shown that the acceptance component of mindfulness reduces anxiety, and, in turn, lower anxiety improves sleep quality. The purpose of this cross-sectional study was to assess changes in mindfulness traits, sleep–wake quality, and general distress, before, during, and after the first COVID-19 wave, testing the model in which acceptance influences sleep through anxiety in each period. A total of 250 participants were recruited before (Pre-Lockdown group: 69 participants, 29 females, 33.04 ± 12.94 years), during (Lockdown group: 78 participants, 59 females, 29.174 ± 8.50 years), and after (After-Lockdown group: 103 participants, 86 females, 30.29 ± 9.46 years) the first Italian lockdown. In each group, self-report questionnaires, assessing mindfulness facets, distress, and sleep–wake quality, were administered and assessed. The Lockdown group reported lower acceptance and higher depression, while the After-Lockdown group reported lower sleep–wake quality and higher anxiety. The results of the path analysis confirmed that higher acceptance reduced anxiety and higher anxiety decreased sleep–wake quality in all groups. Our results confirm that acceptance influences sleep through the mediating role of anxiety. Full article

The current study investigates the impact of sleep loss on neurobehavioral functioning and sleepiness in a natural setting among healthy adolescents. Fifty-nine adolescents (32 females) from grades 7 to 12 (mean age of 16.29 ± 1.86 years) participated in the study. All participants wore the actigraph for a continuous five to seven days, including school and nonschool days. Subjective sleepiness and neurobehavioral performance (using the psychomotor vigilance test and the digit symbol substitution test) were measured three times a day on two school days and one nonschool day. The results presented that sleep loss influenced subjective sleepiness reports, showing higher sleepiness scores following sleep loss than following sufficient night sleep. Neurobehavioral functioning across all measurements was also significantly worse following sleep loss. Furthermore, participants performed worse on weekday morning assessments than on assessments at other times of the day following sleep loss. These findings suggest that sleep loss in natural settings has a significant impact on neurobehavioral performance and subjective sleepiness. Our findings have essential implications for public policy on school schedules. Full article

Many medicinal plants have been used in Asia for treating a variety of mental diseases, including insomnia and depression. However, their sedative–hypnotic effects and mechanisms have not been clarified yet. Accordingly, the objective of this study was to investigate the sedative–hypnotic effects of water extracts of five medicinal plants: Coptidis Rhizoma, Lycii Fructus, Angelicae sinensis Radix, Bupleuri Radix, and Polygonum multiflorum Thunberg. The binding abilities of five medicinal plant extracts to the GABA_A–BZD and 5-HT_2C receptors were compared. Their abilities to activate arylalkylamine N-acetyltransferase (AANAT), a melatonin synthesis enzyme, in pineal cells were also determined. Following in vitro tests, the sedative and hypnotic activities of extracts with the highest activities were determined in an animal sleep model. In the binding assay, the water extracts of Coptidis Rhizoma (WCR) showed high binding affinity to the GABA_A–BZD and 5-HT_2C receptors in a dose-dependent manner. Additionally, WCR increased the AANAT activity up to five times compared with the baseline level. Further animal sleep model experiments showed that WCR potentiated pentobarbital-induced sleep by prolonging the sleep time. It also decreased the sleep onset time in mice. In addition, WCR reduced wake time and increased non-rapid eye movement (NREM) sleep without EEG power density (percentages of δ, θ, and α waves) during NREM sleep in rats. WCR could effectively induce NREM sleep without altering the architectural physiologic profile of sleep. This is the first report of the sedative–hypnotic effect of Coptidis Rhizoma possibly by regulating GABA_A and 5-HT_2C receptors and by activating AANAT activity. Full article

Objective: This study evaluated the effectiveness of a parent-focused intervention aimed at the promotion of healthy sleep patterns and controlled exposure to electronic media (EM) in young adolescents. Participants: The sample included 70 dyads of parents (68 mothers and 2 fathers) and adolescents. Intervention and control groups each consisted of 35 young adolescents with a mean age of 10.7 (0.9) years old. Methods: Three waves of data collection included baseline, post-intervention, and 3 month follow-up. In each wave, adolescents reported habitual electronic media exposure and sleep patterns for a week and wore an actigraph for five nights. Parents in the intervention group participated in a six-session interactive workshop, while parents in the control group received equivalent written information by mail. Results: The intervention led to earlier bedtimes (p < 0.001), increased sleep efficiency (p < 0.01), increased sleep duration (p < 0.001) and reduced video games exposure (p < 0.01). Benefits were maintained at the follow-up. Conclusion: Interventions tailored for parents can create lasting positive changes in sleep patterns and EM exposure in young adolescents. Full article

Growing evidence indicates an association between reduced dream recall and depressive symptomatology. Here, we tested the prediction that reduced dream recall in individuals experiencing major depressive disorder (MDD) is due to alterations in circadian and sleep processes. Nine young healthy women (20–31 years) and eight young unmedicated women (20–31 years) diagnosed with MDD underwent a 40 h multiple nap protocol with ten alternating cycles of 150 min wake/75 min sleep under a stringently controlled circadian laboratory protocol. After each nap, we assessed dream recall, number of dreams and dream emotional load using the Sleep Mentation Questionnaire. Dream recall and the number of dreams did not significantly differ between groups (pFDR > 0.1). However, there was a significant difference for the dream emotional load (interaction of “Group” vs. “Time”, pFDR = 0.01). Women with MDD had a two-fold higher (negative) emotional load as compared to healthy control women, particularly after naps during the circadian night (between ~22:00 h and ~05:00 h; Tukey–Kramer test, p = 0.009). Furthermore, higher (negative) dream emotional load was associated with impaired mood levels in both groups (R² = 0.71; p < 0.001). Our findings suggest that the circadian and sleep modulation of dreaming may remain intact in unmedicated young women experiencing MDD. Full article

Sleep disorders have been related to body weight, social conditions, and a number of comorbidities. These include high blood pressure and type 2 diabetes, both of which are prevalent in the First Nations communities. We explored relationships between obstructive sleep apnea (OSA) and risk factors including social, environmental, and individual circumstances. An interviewer-administered survey was conducted with adult participants in 2018–2019 in a First Nations community in Saskatchewan, Canada. The survey collected information on demographic variables, individual and contextual determinants of sleep health, and objective clinical measurements. The presence of OSA was defined as an apnea–hypopnea index (AHI) ≥5. Multiple ordinal logistic regression analysis was conducted to examine relationships between the severity of OSA and potential risk factors. In addition to the survey, 233 men and women participated in a Level 3 one-night home sleep test. Of those, 105 (45.1%) participants were reported to have obstructive sleep apnea (AHI ≥ 5). Mild and moderately severe OSA (AHI ≥ 5 to <30) was present in 39.9% and severe OSA (AHI ≥ 30) was identified in 5.2% of participants. Being male, being obese, and snoring loudly were significantly associated with severity of OSA. The severity of OSA in one First Nation appears relatively common and may be related to mainly individual factors such as loud snoring, obesity, and sex. Full article

Specific noises (e.g., traffic or wind turbines) can disrupt sleep and potentially cause a mismatch between subjective sleep and objective sleep (i.e., “sleep misperception”). Some individuals are likely to be more vulnerable than others to noise-related sleep disturbances, potentially as a result of increased pre-sleep cognitive arousal. The aim of the present study was to examine the relationships between pre-sleep cognitive arousal and sleep misperception. Sixteen healthy sleepers participated in this naturalistic, observational study. Three nights of sleep were measured using actigraphy, and each 15-s epoch was classified as sleep or wake. Bedside noise was recorded, and each 15-s segment was classified as containing noise or no noise and matched to actigraphy. Participants completed measures of habitual pre-sleep cognitive and somatic arousal and noise sensitivity. Pre-sleep cognitive and somatic arousal levels were negatively associated with subjective–objective total sleep time discrepancy (p < 0.01). There was an association between sleep/wake and noise presence/absence in the first and last 90 min of sleep (p < 0.001). These results indicate that higher levels of habitual pre-sleep arousal are associated with a greater degree of sleep misperception, and even in healthy sleepers, objective sleep is vulnerable to habitual bedside noise. Full article

Socioeconomic status (SES) has an unrecognized influence on behavioral risk factors as well as public health strategies related to sleep health disparities. In addition to that, objectively measuring SES’ influence on sleep health is challenging. A systematic review of polysomnography (PSG) studies investigating the relation between SES and sleep health disparities is worthy of interest and holds potential for future studies and recommendations. A literature search in databases was conducted following Prisma guidelines. Search strategy identified seven studies fitting within the inclusion criteria. They were all cross-sectional studies with only adults. Except for one study conducted in India, all of these studies took place in western countries. Overall emerging trends are: (1) low SES with its indicators (income, education, occupation and employment) are negatively associated with PSG parameters and (2) environmental factors (outside noise, room temperature and health worries); sex/gender and BMI were the main moderators of the relation between socioeconomic indicators and the variation of sleep recording with PSG. Socioeconomic inequalities in sleep health can be measured objectively. It will be worthy to examine the SES of participants and patients before they undergo PSG investigation. PSG studies should always collect socioeconomic data to discover important connections between SES and PSG. It will be interesting to compare PSG data of people from different SES in longitudinal studies and analyze the intensity of variations through time. Full article

Sleep and circadian rhythms are closely involved in the immune system and its regulation. Here, we describe this relationship and provide recommendations regarding the influence of sleep and circadian rhythms on vaccination success. We review studies investigating how viral susceptibility is influenced by changes in immunological parameters as a consequence of sleep deprivation. Short sleep duration and poor sleep efficiency both appear to be strong factors leading to greater vulnerability. In addition, both sleep duration and the time of day of the vaccination seem to be associated with the magnitude of the antibody response after vaccination. Based on these findings, a recommendation would consist of a sleep duration of 7 h or more every night to both reduce the risk of infection and to optimize the efficacy of vaccination with respect to circadian timing. Improving sleep quality and its circadian timing can potentially play a role in preventing infection and in vaccination benefits. In conclusion, sufficient (or longer) sleep duration is important in both reducing susceptibility to infection and increasing antibody response after vaccination. Full article

While the early identification of insomnia in patients with schizophrenia is of clinical relevance, the use of specific compounds to treat insomnia has been studied less in postmenopausal women with schizophrenia. We aimed to explore the effects of melatonin, sex hormones, and raloxifene for the treatment of insomnia in these populations. Although melatonin treatment improved the quality and efficiency of the sleep of patients with schizophrenia, few studies have explored its use in postmenopausal women with schizophrenia. The estrogen and progesterone pathways are dysregulated in major psychiatric disorders, such as in schizophrenia. While, in the context of menopause, a high testosterone-to-estradiol ratio is associated with higher frequencies of depressive symptoms, the effects of estradiol and other sex hormones on sleep disorders in postmenopausal women with schizophrenia has not been sufficiently investigated. Raloxifene, a selective estrogen receptor modulator, has shown positive effects on sleep disorders in postmenopausal women. Future studies should investigate the effectiveness of hormonal compounds on insomnia in postmenopausal women with schizophrenia. Full article

Both sleep-wake behavior and circadian rhythms are tightly coupled to energy metabolism and food intake. Altered feeding times in mice are known to entrain clock gene rhythms in the brain and liver, and sleep-deprived humans tend to eat more and gain weight. Previous observations in mice showing that sleep deprivation (SD) changes clock gene expression might thus relate to altered food intake, and not to the loss of sleep per se. Whether SD affects food intake in the mouse and how this might affect clock gene expression is, however, unknown. We therefore quantified (i) the cortical expression of the clock genes Per1, Per2, Dbp, and Cry1 in mice that had access to food or not during a 6 h SD, and (ii) food intake during baseline, SD, and recovery sleep. We found that food deprivation did not modify the SD-incurred clock gene changes in the cortex. Moreover, we discovered that although food intake during SD did not differ from the baseline, mice lost weight and increased food intake during subsequent recovery. We conclude that SD is associated with food deprivation and that the resulting energy deficit might contribute to the effects of SD that are commonly interpreted as a response to sleep loss. Full article

Neurobehavioral task performance is modulated by the circadian and homeostatic processes of sleep/wake regulation. Biomathematical modeling of the temporal dynamics of these processes and their interaction allows for prospective prediction of performance impairment in shift-workers and provides a basis for fatigue risk management in 24/7 operations. It has been reported, however, that the impact of the circadian rhythm—and in particular its timing—is inherently task-dependent, which would have profound implications for our understanding of the temporal dynamics of neurobehavioral functioning and the accuracy of biomathematical model predictions. We investigated this issue in a laboratory study designed to unambiguously dissociate the influences of the circadian and homeostatic processes on neurobehavioral performance, as measured during a constant routine protocol preceded by three days on either a simulated night shift or a simulated day shift schedule. Neurobehavioral functions were measured every 2 h using three functionally distinct assays: a digit symbol substitution test, a psychomotor vigilance test, and the Karolinska Sleepiness Scale. After dissociating the circadian and homeostatic influences and accounting for inter-individual variability, peak circadian performance occurred in the late biological afternoon (in the “wake maintenance zone”) for all three neurobehavioral assays. Our results are incongruent with the idea of inherent task-dependent differences in the endogenous circadian impact on performance. Rather, our results suggest that neurobehavioral functions are under top-down circadian control, consistent with the way they are accounted for in extant biomathematical models. Full article

The purpose of this study was to investigate the self-reported risk of obstructive sleep apnea syndrome (OSAS) in the municipality of Thessaly, Greece, and the level of awareness of both the disease and its diagnosis. Inhabitants of Thessaly (254 total; 84 men and 170 women) were studied by means of questionnaires via a telephone-randomized survey. This comprised: (a) the Berlin questionnaire for evaluation of OSAS risk; (b) the evaluation of daytime sleepiness by the Epworth Sleepiness Scale; and (c) demographic and anthropometric data. The percentage of participants at high risk for OSA was 26.77%, and the percentage of people who were at high risk of excessive daytime sleepiness was 10.63%. High risk for OSAS was found to be 3.94%. No significant differences were found between high- and low-risk OSAS participants associated with age, smoking and severity of smoking. Regarding the knowledge of the community about OSAS, the majority of the sample was aware of the entity (64.17%), while fewer had knowledge about the diagnosis (18.50%) and polysomnography (24.80%). The high risk of OSA prevalence and the low awareness of the diagnosis of OSA highlights the need for the development of health promotion programs aiming at increasing the disease awareness in the general population in order to address OSA more effectively. Full article

The effect of cortisol on dreams has been scarcely studied. The aim of this exploratory study was to assess the possible effect of cortisol levels on dream recall/affect, considering, in female subjects, their menstrual cycle phase. Fifteen men and fifteen women were recruited. Saliva samples were used for the detection of cortisol levels. Participants were instructed to provide four saliva samples, during three consecutive days. After awakening, on the second and third day, they were asked whether they could recall the previous night’s dreams and whether these were pleasant or unpleasant. Female subjects followed this procedure twice: firstly, during the luteal phase and, secondly, during the follicular phase of the menstrual cycle. Subjects with higher evening or higher morning cortisol levels tended to show increased dream recall; a non-statistically significant association between morning cortisol levels and positive dream affect was also found. This association acquired statistical significance for salivary morning cortisol levels exceeding the upper normal level of 19.1 nmol/L (OR: 4.444, 95% CI: 1.108–17.830, p-value: 0.039). No connection between menstrual cycle stages and dream recall/affect was detected. In conclusion, cortisol may be a crucial neuromodulator, affecting dream recall and content. Therefore, its effects on sleep and dreams should be further studied. Full article

This study aimed to determine the effect of sleep quantity and quality via the Pittsburgh Sleep Quality Index (PSQI) on students’ academic achievement in their first year of university study. In this cross-sectional study, 193 students (102 female, 91 male, mean ± SD; age = 19.3 ± 2.9 y) from an undergraduate Health degree in New Zealand completed the PSQI four weeks prior to the end of the semester in their first year of university study. Results from three core subjects in the first semester were averaged and correlations between the PSQI and academic success were evaluated using Spearman’s rho (ρ). The group were also trichotomized using a PSQI global score of ≤5 as the threshold for “good” sleepers (n = 62, 32%), a score of 5–8 for “moderate” sleepers (n = 63, 33%) and a score ≥8 to characterize “poor” sleepers (n = 68, 35%). Overall, students averaged 7 h 37 min of self-reported sleep duration with an average bedtime of 22:55 p.m. and wake time of 8:01 a.m. There was a significant, small inverse relationship between academic performance and bedtime (p = 0.03, ρ = −0.14), with those going to bed earlier having superior academic success. The trichotomized data demonstrated no significant differences in academic performance between students with poor, moderate and good sleep quality (p = 0.92). Later bedtimes were associated with lower academic performance in a group of first year university students. However, there were no other relationships observed between academic success and self-reported sleep quality or quantity as determined by the PSQI. Enhancing awareness of the impact of sleep timing on academic success should be prioritized and strategies to improve sleep hygiene should be promoted to university students. Full article