Clocks & Sleep

The effect of caffeine on the behavior and sleep patterns of zebrafish larvae, as well as its underlying mechanisms, has been a topic of great interest. This study aimed to investigate the impact of caffeine on zebrafish larval sleep/wake behavior and the expression of key regulatory genes such as cAMP-response element binding protein (CREB) and adenosine (ADA) in the sleep pathway. To begin, the study determined the optimal dose and duration of caffeine exposure, with the optimal doses found to be 31.25 μM, 62.5 μM, and 120 μM. Similarly, the optimal exposure time was established as no more than 120 h, ensuring a mortality rate of less than 10%. The confirmation of these conditions was achieved through the assessment of angiogenesis and the inflammatory reaction. As a result, the treatment time point of 24 h post-fertilization (hpf) was selected to examine the effects of caffeine on zebrafish larval sleep rhythm (48 h, with a light cycle of 14:10). Furthermore, the study analyzed the expression of clock genes (bmal1a, per1b, per2, per3, cry2), adenosine receptor genes (adora1a, adora1b, adora2aa, adora2ab, adora2b), and key regulatory factors (CREB and ADA). The research confirmed that caffeine could induce sleep pattern disorders, significantly upregulate adenosine receptor genes (adora1a, adora1b, adora2a, adora2ab, adora2b) (p < 0.05), and markedly decrease the total sleep time and sleep efficiency of the larvae. Additionally, the activity of ADA significantly increased during the exposure (p < 0.001), and the tissue-specific expression of CREB was also significantly increased, as assessed by immunofluorescence. Caffeine may regulate circadian clock genes through the ADA/ADORA/CREB pathway. These findings not only enhance our understanding of the effects of caffeine on zebrafish larvae but also provide valuable insights into the potential impact of caffeine on human behavior and sleep. Full article

Background: Several environmental factors affect sleep. We investigated the sleep and sleep-related habits of preschool children living in Tibet and conducted an international comparison with those in Japan. Methods: We conducted a community-based cross-sectional study using the Chinese version of the Japanese Sleep Questionnaire for Preschoolers (JSQ-P-C) and compared the results with previous data on Japanese children. Results: The sleep status of 3113 children aged 3–6 years old in Qinghai province was evaluated. The average wake time and bedtime of the Tibetan children were 7:20 ± 0:31 and 21:16 ± 0:43, respectively. Their mean nocturnal sleep duration was 10.0 ± 0.7 h. In comparing 3-year-old children, the time for which they viewed TV in Tibet was shorter (65.5 ± 44.6 min) than that in Japan (149.7 ± 76.6 min), and the mother’s bedtime was earlier in Tibet (21:28 ± 2:14) than in Japan (23:20 ± 1:05). However, the bedtime and sleep duration of the Tibetan children (21:17 ± 0:37 and 10.0 ± 0.7 h) were fairly similar to those of the Japanese children (21:24 ± 1:57 and 9.8 ± 0.8 h). Conclusions: The late bedtime and short nocturnal sleep duration of Tibetan toddlers were the same as those of Japanese toddlers despite considerable differences in their lifestyle and environment. Full article

In this study, we investigated the sleep–wake rhythm of nursery school children with the aim of supporting their health and mental/physical development. We analyzed 4881 children from infancy to 6 years of age, using 2 week sleep tables recorded by their guardians. The tables contained night bedtimes, wake times, nighttime/daytime sleep duration, and the differences in these between weekdays and weekends. The total sleep decrement of children with increasing age is attributed to a decrease in daytime sleep, while nighttime sleep duration remains almost unchanged at about 10 h, which is, therefore, referred to as the nighttime basic sleep duration (NBSD). Although bedtime stabilizes at around 9:30 p.m. by the age of 2, wake-up times tend to be before 7 a.m., which results in sleep insufficiency during weekdays. This lack of sleep is compensated for by long naps on weekdays and by catching up on sleep on weekend mornings, which may contribute to future social jet lag. Guardians are encouraged to know their children’s exact NBSD and set an appropriate bedtime to be maintained on weekdays. This helps to prevent sleep debt and fosters a consistent daily rhythm of waking up at the same time both on weekdays and weekends. These conditions are believed to support mental/physical development and school and social adaptation. Full article

The need for sleep is universal, and the ability to meet this need impacts the quality of life for patients, families, and caregivers. Although substantial progress has been made in treating rare diseases, many patients have unmet medical sleep needs, and current regulatory policy makes it prohibitively difficult to address those needs medically. This opinion reviews the rare disease experience with sleep disorders and explores potential solutions. First, we provide case profiles for the rare diseases Wilson’s Disease, Angelman Syndrome, and Prader–Willi Syndrome. These profiles highlight challenges in rare disease diagnosis and barriers to pinpointing disease pathophysiology, including biomarkers that intersect with sleep disorders. Second, we transition to a bird’s eye view of sleep disorders and rare diseases by reporting input from a stakeholder discussion with the U.S. Food and Drug Administration regarding abnormal sleep patterns in various rare diseases. Last, in response to the profound unmet medical needs of patients with rare diseases and sleep disorders, we propose adapting and using the clinical trial design known as a “basket trial”. In this case, a basket trial would include patients with different rare diseases but the same debilitating symptoms. This research approach has the potential to benefit many rare disease patients who are otherwise left with profound unmet medical needs. Full article

In many medical settings, medications are typically administered in the morning or evening, aligning with patients’ daily routines. This practice does not stem from chronotherapy, which involves scheduling drug administration to enhance its effectiveness, but rather from the way clinical operations are structured. The timing of drug administration can significantly affect a medication’s effectiveness and side effects, with the impact varying by up to ten times based on circadian rhythms. Disorders such as major depression, bipolar disorder, and schizophrenia are linked to disruptions in these rhythms. Recent studies have found that circadian dysfunctions, including genetic and neurohumoral changes, underlie many psychiatric conditions. Issues such as an altered glucocorticoid rhythm due to impaired HPA axis function, disturbed melatonin balance, and sleep disturbances have been noted in psychotic disorders. Furthermore, mood disorders have been associated with changes in the expression of circadian rhythm genes such as Clock, Bmal1, and Per. Considering that the absorption, biodistribution, effects on target organs, half-life, metabolism, and elimination of drugs are all influenced by the body’s circadian rhythms, this narrative review explores the optimal timing of medication administration to maximize efficacy and minimize side effects in the treatment of psychiatric disorders. By closely monitoring circadian variations in cortisol, melatonin, and key clock genes, as well as by deepening our understanding of the metabolisms and pharmacokinetics of antipsychotic medications, we propose a chronotherapy approach for psychiatric patients that could significantly enhance patient care. Full article

Understanding user challenges with light dosimeters is crucial for designing more acceptable devices and advancing light exposure research. We systematically evaluated the usability and acceptability of a light dosimeter (lido) with 29 participants who wore the dosimeter near the corneal plane of the eye for 5 days. Common reasons for not wearing the dosimeter included exercise, recharging, wet environments, public places, and discomfort. Despite these issues, participants adhered to using the dosimeter with high compliance (89% of recording time). Our findings revealed a significant discrepancy between mean (300 lx_mEDI) and median (51 lx_mEDI) melanopic equivalent daylight illuminance. This discrepancy indicates that the participants were exposed to significantly lower light levels most of the time. Specifically, participants were exposed to light levels above 250 lx_mEDI for only 14% of their wearing time. This highlights the need for increased exposure to recommended light levels. In the evening, participants were exposed to less than the recommended 10 lx_mEDI for 58% of their wearing time, which is in line with the guidelines for reducing light exposure before sleep. This study highlights the urgent need for strategies to increase daily light exposure that are more in line with circadian health recommendations. Full article

Cognitive fatigue (CF) is a critical factor affecting performance and well-being. It can be altered in suboptimal sleep quality conditions, e.g., in patients suffering from obstructive sleep apnea who experience both intermittent hypoxia and sleep fragmentation (SF). Understanding the neurophysiological basis of SF in healthy individuals can provide insights to improve cognitive functioning in disrupted sleep conditions. In this electroencephalographical (EEG) study, we investigated in 16 healthy young participants the impact of experimentally induced SF on the neurophysiological correlates of CF measured before, during, and after practice on the TloadDback, a working memory task tailored to each individual’s maximal cognitive resources. The participants spent three consecutive nights in the laboratory two times, once in an undisrupted sleep (UdS) condition and once in an SF condition induced by non-awakening auditory stimulations, counterbalanced and performed the TloadDback task both in a high (HCL) and a low (LCL) cognitive load condition. EEG activity was recorded during wakefulness in the 5 min resting state immediately before and after, as well as during the 16 min of the TloadDback task practice. In the high cognitive load under a sleep-fragmentation (HCL/SF) condition, high beta power increased during the TloadDback, indicating heightened cognitive effort, and the beta and alpha power increased in the post- vs. pre-task resting state, suggesting a relaxation rebound. In the low cognitive load/undisturbed sleep (LCL/UdS) condition, low beta activity increased, suggesting a relaxed focus, as well as mid beta activity associated with active thinking. These findings highlight the dynamic impact of SF on the neurophysiological correlates of CF and underscore the importance of sleep quality and continuity to maintain optimal cognitive functioning. Full article

For centuries, epileptic seizures have been noticed to recur with temporal regularity, suggesting that an underlying biological rhythm may play a crucial role in their timing. In this review, we propose to adopt the framework of chronobiology to study the circadian timing of seizures. We first review observations made on seizure timing in patients with epilepsy and animal models of the disorder. We then present the existing chronobiology paradigm to disentangle intertwined circadian and sleep–wake timing mechanisms. In the light of this framework, we review the existing evidence for specific timing mechanisms in specific epilepsy syndromes and highlight that current knowledge is far from sufficient. We propose that individual seizure chronotypes may result from an interplay between independent timing mechanisms. We conclude with a research agenda to help solve the urgency of ticking seizures. Full article

Insomnia is a common sleep complaint in Canada and is associated with increased use of health care services and economic burden. This paper examines the association of insomnia with functional outcomes relevant to daily behaviors and sleep-related quality of life among First Nations participants using the Functional Outcomes of Sleep Questionnaire (FOSQ-10). The First Nations Sleep Health Project follow-up survey was conducted in partnership with two Cree First Nations in the summer of 2022, where 355 individuals participated. Statistical analysis was conducted using logistic regression models. The mean age of the participants was 40.76 ± 14.60 (SD) years, and 59.4% were females. The prevalence of chronic insomnia (Insomnia Severity Index score of ≥15) was 21.0%, with more females (26.1%) than males (13.8%) experiencing it among the 348 participants. Overall, the mean FOSQ-10 score was 17.27 ± 2.98 among the 350 participants, with those who had clinical insomnia reporting significantly lower scores than those without clinical insomnia (mean ± SD: 14.6 ± 3.9 vs. 18.0 ± 2.1; p < 0.001). The FOSQ-10 scores indicated sleep-related functional impairment (FOSQ-10 total score < 17.90) in 46.6% of participants. After adjusting for age, excessive daytime sleepiness, sex, and regular use of prescription medication, we found that clinical insomnia was significantly associated with functional impairments. In fact, a person with clinical insomnia was 3.5 times more likely to have functional impairments than those without clinical insomnia. This study highlights the significant association between insomnia and functional impairments related to daily behaviors and quality of life in two First Nation communities. Identifying this association can help healthcare providers to diagnose and treat patients with insomnia in these communities. Full article

There is a growing body of evidence regarding the clinical significance of PLMS, and this movement disorder is of concern in both clinical and scientific contexts. Leg actigraphy is a convenient and promising method for screening periodic limb movements in sleep (PLMSs). This study aims to demonstrate the reliability of the SOMNOwatch™ actigraph for detecting periodic limb movements in sleep. Twenty-eight patients, referred to a sleep laboratory for various sleep problems, underwent nocturnal polysomnography with simultaneous one-sided actigraphy using the SOMNOwatch™ actigraph. Recordings of leg movements obtained from both methods were manually scored, calculating the periodic limb movement index (PLMI). The agreement between the methods was assessed through correlation analysis and event-by-event comparison. The correlation between the PLMI derived from PSG and SOMNOwatch™ was high and statistically significant (r = 0.98, p < 0.0001). The SOMNOwatch™ demonstrated a sensitivity of 86.7% and a specificity of 92.3% in detecting PLMS. Similarly, for detecting patients with a PLMI equal to or greater than 15, the sensitivity was 85.7%, and the specificity was 95.2%. Full article

Adolescence and young adulthood are transitional periods associated with significant changes and challenges, leading to a heightened vulnerability to sleep disturbances and mental health difficulties. This stage is often associated with an increased preference for eveningness, manifested as a later chronotype. The current study aimed to investigate the directionality of the association between chronotype, based on an individual’s sleep–wake behaviour, and insomnia in young people using a two-wave panel design with a 12-month interval. A total of 370 participants aged 15–24 (mean age: 21.0 ± 2.0, 72.7% female) were recruited from local secondary schools and universities. Insomnia symptoms were assessed using the Insomnia Severity Index, while chronotype was measured using the Munich Chronotype Questionnaire. Temporal associations were analysed using a series of cross-lagged panel models. The best fitting and most parsimonious model indicated that a later chronotype at baseline predicts more severe insomnia symptoms at the 12-month follow-up after accounting for autoregressive effects. However, the opposite causal model, where baseline insomnia symptoms predicted the chronotype at the 12-month follow-up, was not supported. These findings suggest that a late chronotype may be a potential risk factor for the development of insomnia in young people, emphasising the importance of considering circadian factors in the prevention and treatment of sleep disturbances among this population. Full article

The present study investigated the effect of acute sleep extension on blood pressure and microvascular vasodilation. Sleep and daily physical activity were objectively measured at home for two weeks using wrist actigraphy in 22 adults (60 ± 15 y). Vascular measurements were made in the morning on the 8th and 15th day. Participants spent at least 10 h in bed on the night prior to one of these testing days to extend sleep. Mean arterial blood pressure (MAP) and peak reactive hyperemia in the forearm were measured on each testing day. Reactive hyperemia and MAP were unaltered (p > 0.05) by sleep extension in the total sample. However, adults who experienced improved sleep efficiency with sleep extension (n = 10, 4.2 ± 1.4%) exhibited reduced MAP (−5.5 ± 4.6 mm Hg, p = 0.005) while adults who had little change or decreased sleep efficiency (n = 12, −1.7 ± 2.9%) showed no change in MAP. The reduction in MAP was significantly different between sleep efficiency groups (p = 0.005, Hedges’ g = 1.21) after adjustment for sex and moderate-to-vigorous physical activity. The results of this study suggest that sleep extension has the potential to reduce blood pressure in midlife to older adults when the additional sleep time improves the quality of sleep. Full article

In this study, we aimed to investigate the relationships between sleep duration and autonomic nervous system (ANS) regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer’s disease who were hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity via the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, hypertension status, and medication use (antipsychotics) as covariates. A sleep duration of 6–9 h per night compared to shorter than 6 h was associated with a greater increase in parasympathetic nervous system activity (p = 0.03), and a sleep duration longer than 9 h was associated with a decrease sympathovagal balance (p = 0.02). In addition, we observed an inverted U-shaped association between sleep duration and ANS regulation. In this pilot study, we demonstrated that a sleep duration of 6–9 h per night may be beneficial for ANS regulation; however, the present study involved only a few participants and had some limitations. Additional research with a larger cohort is needed to confirm these findings. Full article

Sleep disorders increase with age and are known risk factors for several mental and physical diseases. They also significantly contribute to a lower quality of life. Nonpharmaceutical approaches, such as cognitive behavioral therapy for insomnia, sleep hygiene advice, relaxation exercises, and physical activity programs, can be delivered directly to patients via mHealth technologies, thereby increasing the accessibility of such interventions and reducing health care-related costs. This scoping review aims to evaluate the effectiveness of mHealth interventions for improving sleep quality among older adults. Published studies in the last 10 years (2013–2023) were identified by searching electronic medical databases (PubMed, PsycINFO, CINAHL, and Scopus) in July 2023 and were independently reviewed by two different authors. The analysis of the data was performed in 2023. The research retrieved 693 records; after duplicates were removed, 524 articles were screened based on their title and abstract, and 28 of them were assessed in full text. A total of 23 studies were excluded because they did not meet the inclusion criteria in terms of population age (60 years or over) or type of intervention (mHealth-based) or because they addressed secondary insomnia. A total of five studies were included in this review, and all of them reported improvements in subjective sleep quality after the application of the mHealth interventions. Two studies also conducted objective assessments of sleep outcomes using actigraphy, reporting improvements only in some of the variables considered. Despite the limited number of available studies, these results are promising and encourage further research. Full article

The application of far-infrared blankets has shown certain benefits in health promotion and therapy, such as improving blood circulation and alleviating muscle pain. However, the effects of such blankets on increasing deep sleep, reducing blood pressure, enhancing memory, dilating microvessels for blood flow, reducing chronic inflammation, and decreasing fatigue remain to be studied. We aim to investigate the effects of the DAZZEON αSleep^® far-infrared blanket on these indicators. This study adopted a double-blind design, recruiting 24 male participants aged over 45 years, divided into two groups of 12 each: (A) a placebo group and (B) a DAZZEON αSleep^® group. The participants used the blanket every night for two weeks, with sleep records taken using a wearable device and blood pressure, blood oxygen levels, arterial stiffness, and surface temperature measured before and after the intervention. Blood samples were collected for an analysis of inflammation and sleep-related blood indicators (serotonin and melatonin), and exercise tests were conducted to assess fatigue improvement. Compared with before the intervention, the blanket significantly increased changes in grip strength and reaction time. Additionally, it significantly increased blood serotonin, melatonin, and nitric oxide concentrations (p < 0.05), thus significantly increasing deep sleep and REM sleep durations (p < 0.05) and improving subjective sleep quality (p < 0.05). This study confirmed that using the DAZZEON αSleep^® far-infrared blanket for 14 consecutive days helps to improve blood circulation, reduce vascular age and arterial stiffness, increase serotonin and melatonin levels, and improve sleep quality, as well as enhances muscle strength and reaction time. Full article

Sleep quality significantly impacts individuals’ overall health, especially in older adults. Older adults often face comorbid conditions, polypharmacy (the intake of five or more medications per day), and medication non-adherence, which are common among those with sleep disorders. The purpose of this systematic review is to examine the relationship between sleep quality and medication adherence in older adults and to describe the measuring instruments used. A systematic review was performed following the PRISMA guidelines. The PubMed, Scopus, Cochrane Library, and CINAHL databases were screened from January 2024 to March 2024. Nine articles were included in the final synthesis based on the inclusion and exclusion criteria. The review found that poor sleep quality is significantly associated with reduced medication adherence in older adults. The key sleep determinants linked to medication non-adherence include sleep disorders, sleep efficiency, sleep duration, and daytime dysfunctions. Inappropriate medication prescriptions have been associated with reduced sleep efficiency. The tools for assessing sleep quality and medication adherence are predominantly subjective and varied. To address these challenges, a comprehensive geriatric assessment should include investigations into sleep disorders and comorbidity factors. Additionally, nursing educational interventions could be pivotal in improving medication adherence among older adults. Full article

College students often experience sleep–wake alterations. Different factors can contribute to insomnia symptoms in this population. The present study aims at investigating pre-sleep behaviours and strategies used to aid sleep onset in young college students and their association with insomnia symptoms. A total of 548 Italian college students (mean age = 23.48 years, range = 19–30 years, 80.5% female) completed a web-based survey on pre-sleep behaviours and sleep-onset facilitators, insomnia symptoms and sleep hygiene, anxiety and depression, and coping strategies. The use of electronic devices at bedtime and as a sleep-onset facilitator was predominant. Students using specific behaviours as sleep-onset facilitators were characterised by more psychological difficulties and poorer sleep. In multivariable linear regression analysis, the frequency of using medications and melatonin, regardless of motivations, was associated with higher insomnia symptoms. The use of specific sleep-onset facilitators positively correlated with the severity of insomnia symptoms. Many students engage in behaviours that are considered sleep-interfering and that are often employed in an attempt to facilitate sleep onset without benefits. Overall, the motivational factors behind pre-sleep behaviours need to be addressed in preventive programs targeting young college students. Full article

Substance use disorder is a major global health concern, with a high prevalence among adolescents and young adults. The most common substances of abuse include alcohol, marijuana, cocaine, nicotine, and opiates. Evidence suggests that a mismatch between contemporary lifestyle and environmental demands leads to disrupted circadian rhythms that impair optimal physiological and behavioral function, which can increase the vulnerability to develop substance use disorder and related problems. The circadian system plays an important role in regulating the sleep–wake cycle and reward processing, both of which directly affect substance abuse. Distorted substance use can have a reciprocal effect on the circadian system by influencing circadian clock gene expression. Considering the detrimental health consequences and profound societal impact of substance use disorder, it is crucial to comprehend its complex association with circadian rhythms, which can pave the way for the generation of novel chronotherapeutic treatment approaches. In this narrative review, we have explored the potential contributions of disrupted circadian rhythms and sleep on use and relapse of different substances of abuse. The involvement of circadian clock genes with drug reward pathways is discussed, along with the potential research areas that can be explored to minimize disordered substance use by improving circadian hygiene. Full article