The role of the circadian system in the etiology of depression.

Circadian rhythms have evolved in almost all organisms enabling them to anticipate alternating changes in the environment. As a consequence, the circadian clock controls a broad range of bodily functions including appetite, sleep, activity and cortisol levels. The circadian clock synchronizes itself to the external world mainly by environmental light cues and can be disturbed by a variety of factors, including shift-work, jet-lag, stress, ageing and artificial light at night. Interestingly, mood has also been shown to follow a diurnal rhythm. Moreover, circadian disruption has been associated with various mood disorders and patients suffering from depression have irregular biological rhythms in sleep, appetite, activity and cortisol levels suggesting that circadian rhythmicity is crucially involved in the etiology and pathophysiology of depression. The aim of the present review is to give an overview and discuss recent findings in both humans and rodents linking a disturbed circadian rhythm to depression. Understanding the relation between a disturbed circadian rhythm and the etiology of depression may lead to novel therapeutic and preventative strategies.

The sleep, circadian, and cognitive performance consequences of watchkeeping schedules in submariners: A scoping review.

Watchkeeping schedules are essential for maintaining submarine operations, but come with human risk factors including, disrupted sleep, circadian misalignment, and cognitive deficits. There is now an emerging literature examining the strengths and weaknesses of submarine watchkeeping schedules trialled in the field and under simulated laboratory conditions. The aim of this scoping review was to summarise this literature. A systematic search of peer-reviewed journal articles and industry reports listed in MEDLINE, PsychINFO, PubMed, Scopus, Embase and Google Scholar undertaken in May 2023 returned 7298 papers. Following screening procedures, 13 studies were identified for inclusion. The findings revealed that sleep was sufficiently preserved regardless of watchkeeping schedule (total sleep time = 5.46-7.89 h), circadian misalignment was greater for non-24 h schedules, and longer off-watch periods were associated with better cognitive performance. Taken together, when comparing between watchkeeping schedules, the present findings suggest that the 4 h-on/8 h-off and 8 h-on/16 h-off schedules may be a good compromise when balancing human risk factors and operational demands. However, submarines are complex and challenging environments to study and there is a need to expand the literature. More research comparing watchkeeping schedules is needed. Future studies should focus on cognitive performance measures, such as problem-solving, prioritisation and executive decision-making to address present shortcomings, and an examination of sleep and circadian countermeasures to assist with adaptation either initiated pre-deployment or by modifying the submarine environment itself should be considered.

Melatonin Treatment of Circadian Rhythm Sleep-Wake Disorder in Obese Children Affects the Brain-Derived Neurotrophic Factor Level.

BACKGROUND: Previous studies proved that the brain-derived neurotrophic factor (BDNF) is correlated with sleep regulation, yet how BDNF functions and reacts in the melatonin treatment of circadian rhythm sleep-wake disorder (CRSWD) among obese children remain enigmatic. Focusing on CRSWD in obese children, this study monitored their sleep efficiency and serum BDNF level changes during the treatment of melatonin. METHODS: In total, 35 obese children diagnosed with CRSWD were included in this study and administrated melatonin (3 mg/night) for 3 months. Blood samples were collected 24 hours before and after the treatment (08:00, 12:00, 16:00, 20:00, 24:00, and 04:00). Subsequently, the plasma melatonin level and serum BDNF level were measured by enzyme-linked immunosorbent assay. Sleep parameters, including sleep quality, Pittsburgh Sleep Quality Index as well as melatonin and BDNF levels before and after treatment, were recorded to profile the effectiveness and safety of melatonin treatment. RESULTS: Melatonin treatment increased plasma melatonin concentration and restored circadian rhythm. Besides, the serum BDNF level showed a significant increase, representing a strong positive correlation with melatonin concentration (p = 0.026). Patients experienced much-improved sleep efficiency (P < 0.001), with longer actual sleep time (P < 0.001), shorter sleep onset latency, and fewer awakenings after treatment (P < 0.001). Besides, melatonin was well tolerated by patients without producing severe side effects. CONCLUSION: Melatonin treatment effectively improved CRSWD among obese children with their serum BDNF levels increased, indicating that BDNF is a key regulator in CRSWD in obese children. This study may offer theoretical support for melatonin treatment of CRSWD in obese children.

Melatonin supplementation for the treatment of infantile spasms: protocol for a randomised placebo-controlled triple-blind trial.

INTRODUCTION: Infantile spasms (IS) is a type of severe epileptic encephalopathy that occurs in infancy and early childhood. IS is characterised clinically by epileptic spasms, often accompanied by sleep disorder and abnormal circadian rhythm. The endogenous circadian rhythm disorder, in turn, can make spasms worse. Melatonin has also been found to have anticonvulsant and neuroprotective properties by adjusting the circadian rhythm. However, there are lack of relevant studies on controlling IS by using melatonin. This study aims to analyse the therapeutic effect of melatonin supplementation for the treatment of IS. METHODS AND ANALYSIS: This is a triple-blinded (trial participant, outcome assessor and the data analyst), prospective, randomised controlled trial to be conducted in the Department of Paediatrics, The First Medical Center of Chinese PLA General Hospital, Beijing, China from November 2020. Patients (n=70) aged 3 months to 2 years with IS will be recruited in this study after receiving written consent from their parents or guardians. Patients will be randomly divided into two equal groups and treated with a combination of adrenocorticotropic hormone, magnesium sulfate and either melatonin or placebo. Clinical data from the patients in the two groups before and after the treatment will be collected and compared. The primary outcome will be assessed 2 weeks later by seizure diaries and reported as the average reduced rate of spasms frequency. Secondary outcomes include the response rate (the rate of spasms-free), electroencephalogram hypsarrhythmia assessment and the psychomotor development assessment (Denver Developmental Screening Test). Sleep quality and safety will also be assessed. ETHICS AND DISSEMINATION: The protocol for this study was approved by the Ethics Committee of Chinese PLA General Hospital (reference number S2020-337-01) and was reported according to the Standard Protocol Items: Recommendations for Interventional Trials statement. Findings of this research will be disseminated through national and international meetings, conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000036208.

Effect of shift work on fatigue, reaction time and accuracy of nurses in the Department of Neurology: A cross-sectional observational study.

AIMS: The purpose of our study was mainly to explore the effect of different shift work on cognitive and executive performance in a real clinical environment among nurses from China. BACKGROUND: Working in shifts can disrupt circadian rhythm, resulting in reduced sleep duration, which can have a detrimental effect on cognitive function. To provide continuous service for patient care, shift work is often a special requirement for nurses. The Stroop test can be used to measure selective attention and reaction time during executive function. However, there have been limited studies about the effect of shift work on the cognitive performance of nurses by Stroop tests. Additionally, no study has been conducted in nurses working in shifts from China. METHODS: Registered nurses in general ward, Department of Neurology, from West China Hospital of Sichuan University, were eligible and consecutively included if they were simultaneously responsible for the day, evening and night shifts on the shift work schedule. A fatigue questionnaire and Stroop tests were performed for each subject separately before and after three working shifts (morning, evening and night shift) to measure changes in fatigue, reaction time and accuracy. RESULTS: Eighteen registered nurses (4 males and 14 females) were included in our study, with a median age of 25 years old. The fatigue degree was significantly increased after day and evening shifts (p = .015 and <.001, respectively). Compared with those in the preshifts, the reaction time in the neutral task and incongruent task was significantly quicker after the day shift (p = .001, p < .001) and night shift (p = .008, .019). In contrast, the reaction time after the evening shift was mildly increased, although without significance. There was no significant difference in accuracy among the three different working shifts. In addition, there was a negative correlation between the fatigue score and reaction time on the incongruent task in the Stroop test before the day shift (r = -.542, p = .020). The fatigue score in the postday shift was found to be inversely related to working hours in the daytime (r = -.500, p = .034). CONCLUSIONS: Our study showed that increased fatigue was found in nurses after day and evening shifts, and shift work can affect the reaction time after the evening shift. However, there was no significant difference in accuracy and a high level of attention could be maintained among the three working shifts, suggesting a highly developed sense of responsibility in our nurses. IMPLICATIONS FOR NURSING MANAGEMENT: In addition to focusing on the common adverse effects of evening or night shifts on nurses, fatigue in the day shift should be paid special attention to by the leadership in the nursing management. Also, nurse managers can implement specific strategies to reduce fatigue after the day shift by shortening the working hours in the daytime appropriately, setting rest periods in the day shift or dividing nurses into morning and afternoon shifts.

Biological and practical considerations regarding circadian rhythm and mental health relationships among nurses working night shifts: a narrative review and recommendations.

BACKGROUND: Sleep is a vital physiological process regulated by the circadian clock and homeostatic mechanisms. Shift work is necessary to ensure continuity of healthcare provision. Worldwide, nurses work night shifts on a rotational or permanent basis. OBJECTIVE: To analyse the impact of circadian rhythm disruption due to night shift work on the mental wellbeing of nurses. METHODS: The literature search was conducted using PubMed and Scopus electronic databases. Selection criteria include studies published in English between 1997 and 2021 that examined the impact of night-shift work on the mental health of nurses. RESULTS: The searches generated a total of 22 records on the PubMed database, and 9 records on the Scopus database, and a total of 31 studies. 29 papers were identified after removal of duplicates. However, 29 articles were screened based on the review of titles and abstracts. 19 articles were identified for full-test review. Seven papers were included in this review. CONCLUSIONS: Disrupted circadian rhythms and poor sleep quality and quantity have been identified as two of the most significant elements in the long-term effects of night-shift work on nurses' mental health. Strategies and policies to promote workplace health may reduce the occurrence of mental health disorders among night-shift nurses, whether the shifts are rotational or permanent. Nursing supervisors and hospital administrators should consider developing new guidelines to minimize the negative impact of night shift rotations on mental health and the quality of life among nurses.

Digging for data: How sleep is losing out to roster design, sleep disorders, and lifestyle factors.

Shift workers employed at a remote mining operation may experience sleep loss, impaired alertness, and consequently negative health and safety outcomes. This study determined the sleep behaviors and prevalence of risk for sleep disorders among shift workers; and quantified alertness for a roster cycle. Sleep duration was significantly less following; night shift by 77 ± 7 min and day shift by 30 ± 7 min. The wake after sleep onset was less by 23 ± 3 min for night shifts and 22 ± 3 min for day shifts (p < 0.05 for all). The prevalence of risk for sleep apnea was 31%, insomnia was 8%, and shiftwork disorder was 44%. Average alertness for all working hours was 75%. Shiftwork in remote mining operations is a significant factor that leads to sleep loss and reduced alertness, which is exacerbated by the high prevalence of risk for sleep disorders.

The vicious circle between physical, psychological, and physiological characteristics of shift work in nurses: a multidimensional approach.

PURPOSE: To compare physical, psychological, and physiological adaptations between rotating and morning shift health workers using objective and subjective approaches. METHODS: Forty nurses [n = 20 morning shift (MS) group; n = 20 rotating shift (RS) group] were evaluated for anthropometry, body composition, and handgrip strength. Quality of life, depression, fatigue, daytime sleepiness, and sleep quality were assessed with SF-36, Zung Self-Rating Depression Scale (SDS), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and Pittsburgh Sleep Quality Index (PSQI), respectively. Physical activity was assessed by the International Physical Activity Questionnaire (IPAQ) and triaxial accelerometers. Sleep-related data were monitored with sleep actigraphy. Salivary melatonin levels were analyzed before/after sleep, and blood lipid profiles were measured the following morning. RESULTS: The RS group had higher mean BMI and total and abdominal fat and scored lower in the SF-36 (p < 0.01). All nurses showed reduced physical activity levels, which, in the RS group, were negatively correlated with FSS (p = 0.033) and SDS scores (p = 0.025). Poor sleep was revealed in 53% of nurses. The RS group had worse sleep quality by PSQI than the MS group (p = 0.045). PSQI scores were inversely related to SF-36 scores and positively correlated with FSS, BMI, waist circumference, and body fat (p < 0.05). CONCLUSION: RS nurses showed increased body mass and total and abdominal fat along with decreased quality of life and sleep quality compared to MS counterparts. A strong relationship was found between physical, psychological, and physiological domains. Further studies should consider workplace interventions to prevent obesity, promote physical activity, and manage poor sleeping patterns in nurses.

Potential effects of shift work on skin autoimmune diseases.

Shift work is associated with systemic chronic inflammation, impaired host and tumor defense and dysregulated immune responses to harmless antigens such as allergens or auto-antigens. Thus, shift workers are at higher risk to develop a systemic autoimmune disease and circadian disruption with sleep impairment seem to be the key underlying mechanisms. Presumably, disturbances of the sleep-wake cycle also drive skin-specific autoimmune diseases, but epidemiological and experimental evidence so far is scarce. This review summarizes the effects of shift work, circadian misalignment, poor sleep, and the effect of potential hormonal mediators such as stress mediators or melatonin on skin barrier functions and on innate and adaptive skin immunity. Human studies as well as animal models were considered. We will also address advantages and potential pitfalls in animal models of shift work, and possible confounders that could drive skin autoimmune diseases in shift workers such as adverse lifestyle habits and psychosocial influences. Finally, we will outline feasible countermeasures that may reduce the risk of systemic and skin autoimmunity in shift workers, as well as treatment options and highlight outstanding questions that should be addressed in future studies.

Human circadian variations.

Circadian rhythms, present in most phyla across life, are biological oscillations occurring on a daily cycle. Since the discovery of their molecular foundations in model organisms, many inputs that modify this tightly controlled system in humans have been identified. Polygenic variations and environmental factors influence each person's circadian rhythm, contributing to the trait known as chronotype, which manifests as the degree of morning or evening preference in an individual. Despite normal variation in chronotype, much of society operates on a "one size fits all" schedule that can be difficult to adjust to, especially for certain individuals whose endogenous circadian phase is extremely advanced or delayed. This is a public health concern, as phase misalignment in humans is associated with a number of adverse health outcomes. Additionally, modern technology (such as electric lights and computer, tablet, and phone screens that emit blue light) and lifestyles (such as shift or irregular work schedules) are disrupting circadian consistency in an increasing number of people. Though medical and lifestyle interventions can alleviate some of these issues, growing research on endogenous circadian variability and sensitivity suggests that broader social changes may be necessary to minimize the impact of circadian misalignment on health.

Sleep disorders in people with type 2 diabetes and associated health outcomes: a review of the literature.

Sleep disorders are linked to development of type 2 diabetes and increase the risk of developing diabetes complications. Treating sleep disorders might therefore play an important role in the prevention of diabetes progression. However, the detection and treatment of sleep disorders are not part of standardised care for people with type 2 diabetes. To highlight the importance of sleep disorders in people with type 2 diabetes, we provide a review of the literature on the prevalence of sleep disorders in type 2 diabetes and the association between sleep disorders and health outcomes, such as glycaemic control, microvascular and macrovascular complications, depression, mortality and quality of life. Additionally, we examine the extent to which treating sleep disorders in people with type 2 diabetes improves these health outcomes. We performed a literature search in PubMed from inception until January 2021, using search terms for sleep disorders, type 2 diabetes, prevalence, treatment and health outcomes. Both observational and experimental studies were included in the review. We found that insomnia (39% [95% CI 34, 44]), obstructive sleep apnoea (55-86%) and restless legs syndrome (8-45%) were more prevalent in people with type 2 diabetes, compared with the general population. No studies reported prevalence rates for circadian rhythm sleep-wake disorders, central disorders of hypersomnolence or parasomnias. Additionally, several cross-sectional and prospective studies showed that sleep disorders negatively affect health outcomes in at least one diabetes domain, especially glycaemic control. For example, insomnia is associated with increased HbA1c levels (2.51 mmol/mol [95% CI 1.1, 4.4]; 0.23% [95% CI 0.1, 0.4]). Finally, randomised controlled trials that investigate the effect of treating sleep disorders in people with type 2 diabetes are scarce, based on a small number of participants and sometimes inconclusive. Conventional therapies such as weight loss, sleep education and cognitive behavioural therapy seem to be effective in improving sleep and health outcomes in people with type 2 diabetes. We conclude that sleep disorders are highly prevalent in people with type 2 diabetes, negatively affecting health outcomes. Since treatment of the sleep disorder could prevent diabetes progression, efforts should be made to diagnose and treat sleep disorders in type 2 diabetes in order to ultimately improve health and therefore quality of life.

Impact of Shift Work and Long Working Hours on Worker Cognitive Functions: Current Evidence and Future Research Needs.

Particular working conditions and/or organization of working time may cause important sleep disturbances that have been proposed to be predictive of cognitive decline. In this regard, circadian rhythm misalignment induced by exposure to night work or long working hours would be responsible for cognitive impairment. Nevertheless, evidence supporting this correlation is limited and several issues still need to be elucidated. In this regard, we conducted a systematic review to evaluate the association between shift/night work and cognitive impairment and address its main determinants. Information provided by the reviewed studies suggested that night work might have serious immediate negative effects especially on cognitive domains related to attention, memory and response inhibition. Furthermore, cognitive performance would progressively worsen over consecutive night shifts or following exposure to very long work shifts. Otherwise, conflicting results emerged regarding the possible etiological role that night work chronic exposure would have on cognitive impairment. Therefore, circadian rhythm desynchronization, lack of sleep and fatigue resulting from night work may negatively impact worker's cognitive efficiency. However, in light of the considerable methodological variability of the reviewed studies, we proposed to develop a standardized research and evaluation strategy in order to obtain a better and comprehensive understanding of this topic.

[Consequences of sleep deprivation on healthcare workers].

Healthcare workers doing night shifts are at risk of lack of sleep or/and circadian rhythm disturbances. The ability to make complex rational decisions is reduced with sleep deprivation; thus, one should try to take the proper precautions. This can be done by reducing the complexity and decision speed as much as possible at nights. Furthermore, as suggested in this review, several individual and organisational measures can reduce the risk of circadian rhythm disorders and make the body ready for a new shift more quickly. Driving motor vehicles should be avoided after night shifts with insufficient sleep.

Evaluation and Management of Sleep and Circadian Rhythm Disturbance in Cancer.

OPINION STATEMENT: Sleep and circadian rhythm disturbance are among the most commonly experienced symptoms in patients with cancer. These disturbances occur throughout the spectrum of cancer care from diagnosis, treatment, and long into survivorship. The pathogenesis of these symptoms and disturbances is based on common inflammatory pathways related to cancer and its' treatments. The evaluation of sleep and circadian disorders requires an understanding of how these symptoms cluster with other cancer-related symptoms and potentiate each other. A thorough evaluation of these symptoms and disorders utilizing validated diagnostic tools, directed review of clinical information, and diagnostic testing is recommended. Treatment of sleep and circadian disturbance in cancer patients should be based on the findings of a detailed evaluation, including specific treatment of primary sleep and circadian disorders, and utilize integrative and personalised management of cancer-related symptoms through multiple pharmacologic and non-pharmacologic modalities. Recognition, evaluation, and treatment of sleep and circadian rhythm disturbance in cancer may lead to improved symptom management, quality of life, and outcomes.

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.

Demographic, psychological, chronobiological, and work-related predictors of sleep disturbances during the COVID-19 lockdown in Italy.

The first COVID-19 contagion wave caused unprecedented restraining measures worldwide. In Italy, a period of generalized lockdown involving home confinement of the entire population was imposed for almost two months (9 March-3 May 2020). The present is the most extensive investigation aimed to unravel the demographic, psychological, chronobiological, and work-related predictors of sleep disturbances throughout the pandemic emergency. A total of 13,989 Italians completed a web-based survey during the confinement period (25 March-3 May). We collected demographic and lockdown-related work changes information, and we evaluated sleep quality, insomnia and depression symptoms, chronotype, perceived stress, and anxiety using validated questionnaires. The majority of the respondents reported a negative impact of confinement on their sleep and a delayed sleep phase. We highlighted an alarming prevalence of sleep disturbances during the lockdown. Main predictors of sleep disturbances identified by regression models were: female gender, advanced age, being a healthcare worker, living in southern Italy, confinement duration, and a higher level of depression, stress, and anxiety. The evening chronotype emerged as a vulnerability factor, while morning-type individuals showed a lower predisposition to sleep and psychological problems. Finally, working from home was associated with less severe sleep disturbances. Besides confirming the role of specific demographic and psychological factors in developing sleep disorders during the COVID-19 pandemic, we propose that circadian typologies could react differently to a particular period of reduced social jetlag. Moreover, our results suggest that working from home could play a protective role against the development of sleep disturbances during the current pandemic emergency.

Light-based methods for predicting circadian phase in delayed sleep-wake phase disorder.

Methods for predicting circadian phase have been developed for healthy individuals. It is unknown whether these methods generalize to clinical populations, such as delayed sleep-wake phase disorder (DSWPD), where circadian timing is associated with functional outcomes. This study evaluated two methods for predicting dim light melatonin onset (DLMO) in 154 DSWPD patients using ~ 7 days of sleep-wake and light data: a dynamic model and a statistical model. The dynamic model has been validated in healthy individuals under both laboratory and field conditions. The statistical model was developed for this dataset and used a multiple linear regression of light exposure during phase delay/advance portions of the phase response curve, as well as sleep timing and demographic variables. Both models performed comparably well in predicting DLMO. The dynamic model predicted DLMO with root mean square error of 68 min, with predictions accurate to within ± 1 h in 58% of participants and ± 2 h in 95%. The statistical model predicted DLMO with root mean square error of 57 min, with predictions accurate to within ± 1 h in 75% of participants and ± 2 h in 96%. We conclude that circadian phase prediction from light data is a viable technique for improving screening, diagnosis, and treatment of DSWPD.

Current Update on Clinically Relevant Sleep Issues in Parkinson's Disease: A Narrative Review.

Sleep disturbances are among the common nonmotor symptoms in patients with Parkinson's disease (PD). Sleep can be disrupted by nocturnal motor and nonmotor symptoms and other comorbid sleep disorders. Rapid eye movement sleep behavior disorder (RBD) causes sleep-related injury, has important clinical implications as a harbinger of PD and predicts a progressive clinical phenotype. Restless legs syndrome (RLS) and its related symptoms can impair sleep initiation. Excessive daytime sleepiness (EDS) is a refractory problem affecting patients' daytime activities. In particular, during the COVID-19 era, special attention should be paid to monitoring sleep problems, as infection-prevention procedures for COVID-19 can affect patients' motor symptoms, psychiatric symptoms and sleep. Therefore, screening for and managing sleep problems is important in clinical practice, and the maintenance of good sleep conditions may improve the quality of life of PD patients. This narrative review focused on the literature published in the past 10 years, providing a current update of various sleep disturbances in PD patients and their management, including RBD, RLS, EDS, sleep apnea and circadian abnormalities.

Deciphering the Interacting Mechanisms of Circadian Disruption and Alzheimer's Disease.

Alzheimer's disease (AD) is one of the crucial causative factors for progressive dementia. Neuropathologically, AD is characterized by the extracellular accumulation of amyloid beta plaques and intracellular neurofibrillary tangles in cortical and limbic regions of the human brain. The circadian system is one of the many affected physiological processes in AD, the dysfunction of which may reflect in the irregularity of the sleep/wake cycle. The interplay of circadian and sleep disturbances inducing AD progression is bidirectional. Sleep-associated pathological alterations are frequently evident in AD. Understanding the interrelation between circadian disruption and AD may allow for earlier identification of AD pathogenesis as well as better suited approaches and potential therapies to combat dementia. In this article, we examine the existing literature related to the molecular mechanisms of the circadian clock and interacting mechanisms of circadian disruption and AD pathogenesis.