Circadian Variation in the Response to Vaccination: A Systematic Review and Evidence Appraisal.

Molecular timing mechanisms known as circadian clocks drive endogenous 24-h rhythmicity in most physiological functions, including innate and adaptive immunity. Consequently, the response to immune challenge such as vaccination might depend on the time of day of exposure. This study assessed whether the time of day of vaccination (TODV) is associated with the subsequent immune and clinical response by conducting a systematic review of previous studies. The Cochrane Library, PubMed, Google, Medline, and Embase were searched for studies that reported TODV and immune and clinical outcomes, yielding 3114 studies, 23 of which met the inclusion criteria. The global severe acute respiratory syndrome coronavirus 2 vaccination program facilitated investigation of TODV and almost half of the studies included reported data collected during the COVID-19 pandemic. There was considerable heterogeneity in the demography of participants and type of vaccine, and most studies were biased by failure to account for immune status prior to vaccination, self-selection of vaccination time, or confounding factors such as sleep, chronotype, and shiftwork. The optimum TODV was concluded to be afternoon (5 studies), morning (5 studies), morning and afternoon (1 study), midday (1 study), and morning or late afternoon (1 study), with the remaining 10 studies reporting no effect. Further research is required to understand the relationship between TODV and subsequent immune outcome and whether any clinical benefit outweighs the potential effect of this intervention on vaccine uptake.

Stability of social jetlag and sleep timing into the second year of the Covid-19 pandemic: Results from a longitudinal study of a nationally representative adult sample in Ireland.

The early phase of the COVID-19 pandemic has previously been associated with marked changes in sleep/wake timing arising from the imposition of society-wide infection mitigation measures. Such observations are considered of broader significance as they reveal the social pressures that sleep timing normally operates under. In order to assess how persistent such changes were as the COVID-19 pandemic developed, we assessed sleep timing and quality in a longitudinal study of a nationally-representative sample of Irish adults with data collected at two time-points (December 2021 and March 2021). Data on social jetlag and chronotype was derived from the micro Munich Chronotype Questionnaire from 830 and 843 participants who provided data in December 2020 and March 2021 respectively, of which 338 contributed data to both timepoints. Demographics and measures of insomnia symptoms, anxiety, depression and loneliness were also collected, and data was analysed both within-subjects and cross-sectionally within data waves. Social jetlag (the mismatch between sleep timing on "work" and "free" days) and other measures of sleep timing were stable across the two time-points, although insomnia symptoms improved slightly from December 2020 to March 2021. The mean social jetlag at both timepoints was ~ 30 minutes, considerably lesser than reported pre-pandemic levels in similar populations. Multiple regression analysis of cross-sectional data reveals that the timing of midsleep on "free" days was only a weak-to-moderate predictor of social jetlag, whilst hours worked per week was the strongest predictor of social jetlag. Requirement for "face-to-face" contact with the public at work and urban location of residence also emerged as predictors of social jetlag, although insomnia, anxiety and depression symptoms and loneliness rating did not. We conclude that sleep timing changes that occurred during the initial phase of the COVID-19 pandemic persisted into the second year of the pandemic, and these results further illustrate the key roles working practices and other social factors have in shaping social jetlag.

Sleep and daytime functioning in children with tourette syndrome: A two-week case-control study with actigraphy and cognitive assessments.

There is increasing recognition of the high prevalence of sleep issues in children with Tourette syndrome (TS), a condition characterised by motor and vocal tics. Overnight polysomnography (PSG) has been the primary mode of sleep assessment in the TS literature, despite the extensive use of actigraphy in other neurodevelopmental populations. As a result, there are existing research gaps surrounding day-to-day variability of sleep in TS and links to daytime functioning. This study adopts a naturalistic, intensive longitudinal design to examine sleep in children with TS while considering potential links to tic severity and daytime functioning. Participants were 34 children aged between 8 and 12 years (12 with TS, 22 neurotypical controls). Wrist actigraphs tracked sleep-wake cycles across two weeks and a battery of scales and cognitive assessments measured sleep disturbances and daytime functioning. Mixed models using N = 476 nights of actigraphy data found that relative to controls, children with TS had significantly increased time in bed, increased sleep onset latency, reduced sleep efficiency, lower subjective sleep quality, but comparable actual sleep time. Higher self-report tic severity at bedtime did not predict increased sleep onset latency. In the sleep disturbance scale, 83.33 % of children with TS met the clinical cut-off for a sleep disorder. Parent-report emotional, behavioural, and executive difficulties were greater in the TS group relative to controls, but performance on cognitive tasks was comparable between groups. Together, findings highlight sleep disturbances as an important clinical factor to consider in the management of TS, though further research is required to substantiate findings in larger-scale studies. This study demonstrates the feasibility of assessing sleep via actigraphy in children with TS, supporting more widespread use in the future.

"Tell Me More About Your Child's Sleep": A Qualitative Investigation Of Sleep Problems In Children With ADHD.

OBJECTIVE: To investigate parental experiences and perceptions of sleep problems in their children with Attention Deficit Hyperactivity Disorder (ADHD), the perceived impacts of sleep problems and coping strategies deployed by parents. METHODS: Semi-structured interviews with twenty-six parents of pre-adolescent children with a diagnosis of ADHD, followed by thematic analysis of the interview transcripts. RESULTS: Three themes were generated from the data: Children's Sleep Difficulties; Impacts of Children's Sleep; and Improving Children's Sleep. Sleep initiation problems in children with ADHD were commonly reported by parents, were perceived to be linked in a bidirectional manner with executive and emotional problems, and were reported as being disruptive to parental sleep. Some parents reported that their children's sleep problems were the initial prompt that lead to a diagnosis of ADHD. Parents reported utilizing a range of coping strategies to mitigate sleep problems, such as controlling the bedroom sensory environment and using emotional "wind down" as part of the bedtime routine. Some parents endorsed a beneficial effect of melatonin on their children's sleep. CONCLUSIONS: Sleep problems in children with ADHD were perceived as important issues by parents. Equipping parents with evidence-based strategies for the management of their children's sleep may lead to benefits for the children, parents and wider household.

Chronobiology of Parkinson's disease: Past, present and future.

Parkinson's disease is a neurodegenerative disorder predominately affecting midbrain dopaminergic neurons that results in a broad range of motor and non-motor symptoms. Sleep complaints are among the most common non-motor symptoms, even in the prodromal period. Sleep alterations in Parkinson's disease patients may be associated with dysregulation of circadian rhythms, intrinsic 24-h cycles that control essential physiological functions, or with side effects from levodopa medication and physical and mental health challenges. The impact of circadian dysregulation on sleep disturbances in Parkinson's disease is not fully understood; as such, we review the systems, cellular and molecular mechanisms that may underlie circadian perturbations in Parkinson's disease. We also discuss the potential benefits of chronobiology-based personalized medicine in the management of Parkinson's disease both in terms of behavioural and pharmacological interventions. We propose that a fuller understanding of circadian clock function may shed important new light on the aetiology and symptomatology of the disease and may allow for improvements in the quality of life for the millions of people with Parkinson's disease.

Thematic Daily Sleep Routine Analysis of Adults Not in Employment Living with Type 2 Diabetes Mellitus.

BACKGROUND: Day-to-day variations in sleep timing have been associated with poorer glycemic control in type 2 diabetes mellitus, although the factors that influence this sleep timing variability are poorly understood. METHODS: Daily routines of sleep in a sample of seventeen adults with type 2 diabetes mellitus who were either retired or not currently working were examined qualitatively through the application of semi-structured interviews and a thematic analysis of the resulting transcripts. RESULTS: Four themes were identified: "Consistent Sleeping Patterns", "Fluctuating Sleep Timing", "Night-Time Disruptions" and "Lasting Effort Needed with Type Two Diabetes Mellitus". The subthemes reflected that many participants had consistent sleep schedules across the seven-day week, but that a desire to maintain a sense of normality, household routines, television schedules and socializing were associated with different sleep timing on weekends. Active disease monitoring and timed medication taking were not identified as important factors in shaping sleep timing. Nocturia, stress and rumination were identified as important factors linked to disrupted sleep. Sleep was not reported as an issue discussed during routine clinical care. CONCLUSION: Sleep timing in participants appears to be driven by interacting psychosocial and physiological factors, although active disease management does not emerge as a major influence on sleep schedules.

Differences in Sleep Offset Timing between Weekdays and Weekends in 79,161 Adult Participants in the UK Biobank.

Variability in the timing of daily sleep is increasingly recognized as an important factor in sleep and general physical health. One potential driver of such daily variations in sleep timing is different work and social obligations during the "working week" and weekends. To investigate the nature of weekday/weekend differences in the timing of sleep offset, we examined actigraphy records of 79,161 adult participants in the UK Biobank who wore an actiwatch for 1 week. The time of sleep offset was found to be on average 36 min later on weekends than on weekdays, and when this difference was expressed as an absolute value (i.e., irrespective of sleep offset being either later or earlier on weekends), it was 63 min. Younger age, more socioeconomic disadvantage, currently being in employment, being a smoker, being male, being of non-white ethnicity and later chronotype were associated with greater differences in sleep offset between weekdays and weekend days. Greater differences in sleep offset timing were associated with age-independent small differences in cardiometabolic health indicators of BMI and diastolic blood pressure, but not HbA1c or systolic blood pressure. In a subset of participants with Type 2 Diabetes Mellitus, weekday/weekend sleep offset differences were associated weakly with BMI, systolic blood pressure and physical activity. Overall, this study demonstrates potentially substantive differences in sleep offset timings between weekdays and weekends in a large sample of UK adults, and that such differences may have public health implications.

Association of perceptions of artificial light-at-night, light-emitting device usage and environmental noise appraisal with psychological distress, sleep quality and chronotype: A cross sectional study.

Exposure to artificial light-at-night (ALAN) is increasing globally, and there are concerns around how ALAN may impact sleep, psychological and physical health. However, there is a lack of evidence in the literature on how individuals perceive ALAN relative to their sleeping environment and habits, and how such perceptions correspond to objectively assessed night-time illuminance at the level of the residence. This cross-sectional study examined how such perceptions associate with sleep quality, sleep timing, psychological distress and cognitive failures. Further we examined the association between illuminance levels calculated as the biologically-relevant melatonin-suppression index (MSI) and the self-report of perception of ALAN. Five hundred and fifty two adult participants completed a survey addressing perception of ALAN in sleep environment along with the Pittsburgh Sleep Quality Index, Munich Chronotype Questionnaire, Cognitive Failure Questionnaire and the General Health Questionnaire. We report that perception of external ALAN in the sleeping environment was associated with poorer sleep quality, more cognitive failures and greater psychological distress, when controlling for age, sex, house location and MSI. No associations were found between the perception of external ALAN and MSI scores, and MSI scores were not associated with scores on any of the self-report measures. Internal lighting passing into the sleeping environment was associated with poorer sleep quality but not with psychological wellbeing. Habitual use of light-emitting devices was associated with poorer psychological wellbeing but not with sleep quality and sleep timing. Perception of environmental noise annoyance at night was associated with higher psychological distress and poorer quality sleep, and the perception of noise annoyance was associated with perception of ALAN. These results may suggest heightened attentional bias towards ALAN associated with poor sleep quality and higher levels of psychological distress, and highlight the need for more granular approaches in the study of ALAN and sleep and psychological health in terms of levels individual ALAN exposure, and an interpretation that seeks to integrate biological and psychological perspectives.

A Data-Informed Perspective on Public Preferences for Retaining or Abolishing Biannual Clock Changes.

Scientific, public, and political discourse around the perennial changing of the clocks during the transitions into and out of daylight saving time (DST) is a touchstone issue for the translation of fundamental chronobiology into societal impacts. The Society for Research on Biological Rhythms, along with other sleep science bodies, has issued a position statement that advocates for the abolition of the biannual clock changes and the adoption of permanent standard time for the optimization of population circadian health. However, there is a paucity of data on preexisting public perceptions and preferences with regard to these issues. In this perspective, we examine 5 issues that we believe are pertinent for chronobiologists to consider to enable effective advocacy on these policies; in particular, we discuss public preference for permanent DST and steps that may need to be taken to understand this preference. We inform our discussion with reference to cross-sectional studies we undertook in Spring 2020 and Fall 2019, around the transition out of and into DST Ireland. We conclude that there appears to be a gap between existing public perceptions and preferences around the clock changes and chronobiological and sleep science-informed positions, and that the chronobiology community may benefit from interdisciplinary collaboration with colleagues with specific social sciences expertise to most effectively advocate for these research-informed positions.

Temporal associations between insomnia and depression symptoms in adults during the COVID-19 pandemic: A cross-lagged path modelling analysis.

It is well recognised that there is an intimate relationship between sleep and depression, with poor quality or short duration sleep associated with greater symptoms of depression. However, it is not clear from the current evidence base what the temporal relationship is between symptoms of insomnia and depression. Further, it is also unclear how the COVID-19 pandemic may impact on such relationships. In this study we have examined the longitudinal relationships between symptoms of depression and insomnia during the COVID-19 pandemic at two points separated by one year (April/May 2020 and March/April 2021) in a sample of 1032 Irish adults using a cross-lagged paths model. We report that there is a bidirectional relationship across time between depression and insomnia symptoms (ß = -0.115 between Insomnia symptoms and subsequent depression symptoms and ß = -0.163 between depression symptoms and subsequent insomnia symptoms; scales scored in opposite directions), and that these relationships persist when COVID-19 anxiety, age and sex are introduced into the model. Our analyses suggest that during the first year of the COVID-19 pandemic that insomnia symptoms predicted depression symptoms one year later, and conversely that depression symptoms predicted subsequent insomnia symptoms.

An exploratory study of associations between sleep timing variability and cardiometabolic health in middle-aged adults with type 2 diabetes mellitus.

Sleep is increasingly recognised as an important risk factor for metabolic disease, and as an important influence on severity in established metabolic disease. Recent evidence suggests that sleep timing variability (the day-to-day fluctuations of sleep timing) may be an important factor in metabolic diseases such as type 2 diabetes mellitus. In the current study, we explore the associations between measures of sleep timing variability and cardiometabolic measures in a group of healthy middle-aged adults with and without type 2 diabetes mellitus. Healthy controls (N = 27) and adults with well-controlled uncomplicated type 2 diabetes mellitus (N = 30) wore actiwatches for an average of 9 days for objective assessment of sleep timing parameters, and also underwent a detailed clinical assessment. We found greater self-reported social jetlag in the diabetes group, but no groupwise differences in measures of sleep timing variability. In the diabetes patients, HbA1c levels were inversely correlated with variability in the time of sleep onset and midsleep, and with sleep duration. HOMA-IR did not correlate with any sleep timing variability measure, nor were there associations between sleep timing variability and other metabolic biomarkers (cholesterol, LDL, HDL, triglycerides and uric acid). Systolic blood pressure was inversely correlated with actigraphically defined social jetlag in both the control and diabetes groups. The results of this study indicate associations between sleep timing variability and HbA1c, but the direction of these relationships is at variance with some other recent reports. Our results indicate a need for future hypothesis-testing studies to further explore the impact of sleep timing variance on metabolic health.

A Systematic Review of Sleep and Circadian Rhythms in Children with Attention Deficit Hyperactivity Disorder.

OBJECTIVE: Children and adults with ADHD often report sleep disturbances that may form part of the etiology and/or symptomatology of ADHD. We review the evidence for sleep changes in children with ADHD. METHODS: Systematic review with narrative synthesis assessing sleep and circadian function in children aged 5 to 13 years old with a diagnosis of ADHD. RESULTS: 148 studies were included for review, incorporating data from 42,353 children. We found that sleep disturbances in ADHD are common and that they may worsen behavioral outcomes; moreover, sleep interventions may improve ADHD symptoms, and pharmacotherapy for ADHD may impact sleep. CONCLUSION: Sleep disturbance may represent a clinically important feature of ADHD in children, which might be therapeutically targeted in a useful way. There are a number of important gaps in the literature. We set out a manifesto for future research in the area of sleep, circadian rhythms, and ADHD.

Posttraumatic stress disorder, complex PTSD and subtypes of loneliness among older adults.

OBJECTIVES: Research examining the relationship between loneliness and Complex Posttraumatic Stress Disorder (CPTSD) is scarce, particularly among older adults. CPTSD includes the core symptoms of PTSD along with additional symptoms reflecting "disturbances in self-organisation" (DSO). This study examined the cross-sectional relationships between loneliness (emotional and social loneliness) and CPTSD symptoms (i.e., PTSD and DSO symptoms) in older adults. METHODS: Structural equation modelling was used to examine these relationships in a nationally representative sample of US adults aged 60-70 years (n = 456). RESULTS: Controlling for covariates, emotional loneliness was associated with PTSD (ß = 0.31) and DSO (ß = 0.57) symptoms whereas social loneliness was only associated with DSO symptoms (ß = 0.25). The model explained 35.0% of the variance in PTSD symptoms and 71.3% in DSO symptoms. CONCLUSION: These findings have important implications for treating and understanding PTSD/CPTSD and their correlates among older adults.

Effects of societal-level COVID-19 mitigation measures on the timing and quality of sleep in Ireland.

OBJECTIVES: Under usual circumstances, sleep timing is strongly influenced by societal imperatives. The sweeping whole-of-society measures introduced in response to the COVID-19 pandemic may represent a unique opportunity to examine the impact of large-scale changes in work practices on sleep timing. As such, we examined the impact of the travel restrictions and work from home orders imposed in Ireland in March 2020 on sleep timing and quality. METHODS: We utilized a cross-sectional survey deployed shortly after the imposition of restrictions which assessed current and retrospective ratings of sleep timing and quality; the final response set analysed was from 797 adults. Participants completed the ultra-short Munich Chronotype Questionnaire, the Pittsburg Sleep Quality Index, and answered questions pertaining to work status such as working from home during the period of restrictions. RESULTS AND CONCLUSION: There was a significant shift to later sleep start and end times, as well as delayed time of midsleep on both work and free days, during the period of restrictions. Sleep duration was longer for work days, while free day sleep duration was shorter and there was a reduction in social jetlag during the restrictions. Those who worked from home during restrictions had longer sleep duration on work day and had a significantly larger difference in sleep end on work day than "essential" workers who continued to attend their normal place of work.

The Role of the Circadian System in Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterised by the core symptoms of inattention, impulsivity and hyperactivity. Similar to many other neuropsychiatric conditions, ADHD is associated with very high levels of sleep disturbance. However, it is not clear whether such sleep disturbances are precursors to, or symptoms of, ADHD. Neither is it clear through which mechanisms sleep and ADHD are linked. One possible link is via modulation of circadian rhythms. In this chapter we overview the evidence that ADHD is associated with alterations in circadian processes, manifesting as later chronotype and delayed sleep phase in ADHD, and examine some mechanisms that may lead to such changes. We also interrogate how the circadian clock may be a substrate for therapeutic intervention in ADHD (chronotherapy) and highlight important new questions to be addressed to move the field forward.

Seasonal and daytime variation in multiple immune parameters in humans: Evidence from 329,261 participants of the UK Biobank cohort.

Seasonal disease outbreaks are perennial features of human infectious disease but the factors generating these patterns are unclear. Here we investigate seasonal and daytime variability in multiple immune parameters in 329,261 participants in UK Biobank and test for associations with a wide range of environmental and lifestyle factors, including changes in day length, outdoor temperature and vitamin D at the time the blood sample was collected. Seasonal patterns were evident in lymphocyte and neutrophil counts, and C-reactive protein CRP, but not monocytes, and these were independent of lifestyle, demographic, and environmental factors. All the immune parameters assessed demonstrated significant daytime variation that was independent of confounding factors. At a population level, human immune parameters vary across season and across time of day, independent of multiple confounding factors. Both season and time of day are fundamental dimensions of immune function that should be considered in all studies of immuno-prophylaxis and disease transmission.

Posttraumatic stress disorder and loneliness are associated over time: A longitudinal study on PTSD symptoms and loneliness, among older adults.

Loneliness has a pernicious effect on mental health in later life and is likely to have a bidirectional relationship with psychopathology. However, longitudinal research examining loneliness and posttraumatic stress symptoms among older adults is scarce. This study aimed to examine the longitudinal relationship between different types of loneliness (social and emotional) and posttraumatic stress symptoms. Using two waves of an older adult sample (n = 1,276) from the Longitudinal Aging Study Amsterdam (LASA), this longitudinal relationship was examined using a multivariate two wave-latent change score (2W-LCS) model. There were significant, however, very small increases in both posttraumatic stress symptoms and emotional loneliness over time, whereas, average social loneliness scores did not significantly increase/decrease over time. Changes in both social (ß = .16) and emotional loneliness (ß = .15) were associated with small changes in posttraumatic stress symptoms, consistent with the existence of a longitudinal association between the constructs, net of covariate effects. Results provide evidence of the existence of a longitudinal association between subtypes of loneliness and posttraumatic stress symptoms, among older adults. Results have implications for clinicians who should identify individuals at risk of developing posttraumatic stress symptoms, and for the theory of both posttraumatic stress disorder and loneliness.

Review: Identification and Management of Circadian Rhythm Sleep Disorders as a Transdiagnostic Feature in Child and Adolescent Psychiatry.

OBJECTIVE: Sleep disturbances are highly frequent features in a range of child and adolescent psychiatric conditions. However, it is commonly not clear if such sleep problems represent symptomatic features of, comorbidities of, or risk factors for these conditions. It is believed that underlying dysfunction in the daily biological (circadian) clock may play important roles in the etiology of many sleep disorders, and circadian rhythm changes are reported in a number of neuropsychiatric conditions. The aim of this review was to explore the key identifying features of circadian rhythm disorders (CRDs) in child and adolescent psychiatry and address how such disorders may be managed in the clinic. METHOD: A narrative review was conducted of the extant literature of CRDs in children and adolescents with psychiatric conditions. RESULTS: Key biological and social factors that contribute to CRDs in children and adolescents, and the cognitive and neurobehavioral consequences resulting from insufficient sleep were outlined. The roles of melatonin and other chronotherapeutic and behavioral interventions for the management of CRDs were also outlined. Further, the importance of careful investigation of circadian rhythm abnormalities in shaping the most effective treatment plan according to chronobiological principles was highlighted. CONCLUSION: CRDs are common in children and adolescents with psychiatric conditions and arise out of complex interactions between biological and social factors. Careful clinical attention to and management of CRDs in child and adolescent psychiatry have the potential for significant benefit not only in the domain of sleep but also in a range of cognitive, affective, and behavioral outcomes.

The impact of the early phase of the COVID-19 pandemic on mental-health services in Europe.

PURPOSE: The current COVID-19 pandemic confronts psychiatric patients and mental health services with unique and severe challenges. METHODS: In order to identify these trans-national challenges across Europe, an ad-hoc survey was conducted among 23 experts, each answering for one European or aligned country. RESULTS: A number of important themes and issues were raised for the impact of COVID-19 on mental health and mental health services, barriers to service provision and future consequences. A number of key issues were reported by colleagues across several jurisdictions, even though these were at different stages of their national epidemics. CONCLUSIONS: Based on these findings, we articulate some important learnings from the early stages of the COVID-19 European pandemic, and highlight key considerations for all countries' mental health services as the current pandemic develops and for future pandemics.

A Cross-Sectional Study of the Associations between Chronotype, Social Jetlag and Subjective Sleep Quality in Healthy Adults.

Social jetlag, a mismatch between internal biological time and social schedules, and a later timing of the midpoint of sleep on work-free days as an indicator of the circadian phase of entrainment (late chronotype), may be factors associated with poor quality sleep. This study examined the association of social jetlag and chronotype with subjective sleep quality ratings in a healthy young adult cohort and interrogated the moderating effects of sex and age on these associations. A total of 1322 participants aged 18 to 40 completed the Pittsburg Sleep Quality Index (PSQI) and the Munich Chronotype Questionnaire. Later timing of midsleep on "free" days (an indicator of chronotype) had a small-to-medium association with poorer subjective sleep quality, independently of sex and age (rho = 0.212, P < 0.001). Greater social jetlag had a small association with poorer subjective sleep quality ratings (rho = 0.077), and this effect was moderated by sex with there being a relationship between social jetlag and sleep quality only in males. Social jetlag did not mediate the relationship between chronotype and sleep quality. These results indicate differential relationships of the chronotype and social jetlag with subjective sleep quality and indicate that sex is a moderating factor for sleep quality's relationship with social jetlag, but not for the association between sleep quality and chronotype.