Circadian disruption and human health

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(19)

Published: Sept. 30, 2021

Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes individual population levels. Evidence points a bidirectional relationship, in that circadian increases disease severity many diseases disrupt rhythms. Importantly, increase the risk for expression development of neurologic, psychiatric, cardiometabolic, immune disorders. Thus, harnessing rich findings from preclinical translational research biology enhance via circadian-based approaches represents unique opportunity personalized/precision medicine overall societal well-being. In this Review, we discuss implications human using bench-to-bedside approach. science applied clinical population-based Given broad regulation health, Review focuses its discussion on selected examples metabolic, cardiovascular, allergic, immunologic disorders highlight interrelatedness between potential interventions, such as bright light therapy exogenous melatonin, well chronotherapy improve and/or modify outcomes.

Language: Английский

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Circadian rhythm sleep–wake disturbances and depression in young people: implications for prevention and early intervention

The Lancet Psychiatry, Journal Year: 2021, Volume and Issue: 8(9), P. 813 - 823

Published: Aug. 19, 2021

Language: Английский

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The sleep–circadian interface: A window into mental disorders

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(9)

Published: Feb. 23, 2024

Sleep, circadian rhythms, and mental health are reciprocally interlinked. Disruption to the quality, continuity, timing of sleep can precipitate or exacerbate psychiatric symptoms in susceptible individuals, while treatments that target sleep-circadian disturbances alleviate psychopathology. Conversely, poor disrupt clock-controlled processes. Despite progress elucidating underlying mechanisms, a cohesive approach integrates dynamic interactions between disorder with both processes is lacking. This review synthesizes recent evidence for dysfunction as transdiagnostic contributor range disorders, an emphasis on biological mechanisms. We highlight observations from adolescent young adults, who at greatest risk developing whom early detection intervention promise benefit. In particular, we aim a) integrate factors implicated pathophysiology treatment mood, anxiety, psychosis spectrum perspective; b) need reframe existing knowledge adopt integrated which recognizes interaction factors; c) identify important gaps opportunities further research.

Language: Английский

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Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi‐disciplinary literature review and agenda for future research from the ISBD task force on chronobiology

Bipolar Disorders, Journal Year: 2021, Volume and Issue: 24(3), P. 232 - 263

Published: Dec. 1, 2021

Symptoms of bipolar disorder (BD) include changes in mood, activity, energy, sleep, and appetite. Since many these processes are regulated by circadian function, rhythm disturbance has been examined as a biological feature underlying BD. The International Society for Bipolar Disorders Chronobiology Task Force (CTF) was commissioned to review evidence neurobiological behavioral mechanisms pertinent BD.Drawing upon expertise animal models, biomarkers, physiology, behavior, CTF analyzed the relevant cross-disciplinary literature precisely frame discussion around disruption BD, highlight key findings, first time integrate findings across levels analysis develop an internally consistent, coherent theoretical framework.Evidence from multiple sources implicates system mood regulation, with corresponding associations BD diagnoses mood-related traits reported genetic, cellular, physiological, domains. However, does not appear be specific is present variety high-risk, prodromal, syndromic psychiatric disorders. Substantial variability ambiguity among definitions, concepts assumptions research have limited replication emergence consensus findings.Future rhythms its role warranted. Well-powered studies that carefully define between BD-related chronobiologically-related constructs, will most illuminating.

Language: Английский

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Circadian biology to advance therapeutics for mood disorders

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(10), P. 689 - 704

Published: Aug. 28, 2023

Mood disorders account for a significant global disease burden, and pharmacological innovation is needed as existing medications are suboptimal. A wide range of evidence implicates circadian sleep dysfunction in the pathogenesis mood disorders, there growing interest these chronobiological pathways focus treatment innovation. We review contemporary three promising areas circadian-clock-based therapeutics disorders: targeting system informed by mechanistic molecular advances; time-tailoring medications; personalizing using parameters. also consider limitations challenges accelerating development new circadian-informed pharmacotherapies disorders.

Language: Английский

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Rapid-acting antidepressants and the circadian clock

Neuropsychopharmacology, Journal Year: 2021, Volume and Issue: 47(4), P. 805 - 816

Published: Nov. 27, 2021

Language: Английский

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Subjective and objective sleep and circadian parameters as predictors of depression-related outcomes: A machine learning approach in UK Biobank

Journal of Affective Disorders, Journal Year: 2023, Volume and Issue: 335, P. 83 - 94

Published: May 6, 2023

Sleep and circadian disruption are associated with depression onset severity, but it is unclear which features (e.g., sleep duration, chronotype) important whether they can identify individuals showing poorer outcomes. Within a subset of the UK Biobank actigraphy mental health data (n = 64,353), penalised regression identified most useful 51 sleep/rest-activity predictors depression-related outcomes; including case-control (Major Depression (MD) vs. controls; postnatal controls) within-case comparisons (severe moderate MD; early later onset, atypical typical symptoms; comorbid anxiety; suicidality). Best models (of lasso, ridge, elastic net) were selected based on Area Under Curve (AUC). For MD controls (n(MD) 24,229; n(control) 40,124), lasso AUC was 0.68, 95 % confidence interval (CI) 0.67–0.69. Discrimination reasonable for symptoms (n(atypical) 958; n(typical) 18,722; ridge: 0.74, CI 0.71–0.77) poor remaining (AUCs 0.59–0.67). Key across included: difficulty getting up, insomnia symptoms, snoring, actigraphy-measured daytime inactivity lower morning activity (~8 am). In distinct 310,718), number these factors shown all Analyses cross-sectional in middle-/older aged adults: comparison longitudinal investigations younger cohorts necessary. measures alone provided to discrimination outcomes, several characteristics that may be clinically useful. Future work should assess alongside broader sociodemographic, lifestyle genetic features.

Language: Английский

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Sleep and circadian rhythm disturbances: plausible pathways to major mental disorders?

World Psychiatry, Journal Year: 2024, Volume and Issue: 23(1), P. 150 - 151

Published: Jan. 12, 2024

The Mental Health Priority Area of the Wellcome Trust recently posited that sleep and circadian rhythm disturbances (SCRDs) are a plausible nexus for linking aspects biology, phenomenology, course treatment major mood, anxiety psychotic disorders1. This emphasis fits well with currently spreading trend to develop more effective scalable forms indicated prevention, early intervention, secondary prevention (of both primary illness progression physical illness). focus on SCRDs also aligns broader studies as why some specific periods life (e.g., adolescence, postnatal, menopause, late life), accompanied by large shifts in 24-hour patterns sleep-wake cycle, associated elevated risk mood disorders2. Along same line, several research groups have now prioritized understanding chronobiology advance management all phases disorders Chronobiology Task Force International Society Bipolar Disorders)3. Developments this area been greatly assisted increased basic biology homeostatic system – recognized Nobel Prize Medicine or Physiology 2017. Of note has delineation molecular architecture core clock, along revelation system's stability is fundamentally regulated common environmental factors, such timing, intensity spectrum light exposure4. It appears there brain circuits mammals which regulates learning activity, not wholly dependent mediation master timekeeper (the suprachiasmatic nucleus), including identified region perihabenular nucleus. discovery new light-sensitive extreme interest clinical psychiatry psychiatric epidemiology. An intriguing finding from over 80,000 adults UK Biobank was exposure artificial at night only rates depression, but an incidence other mental disorders, bipolar disorder, generalized disorder post-traumatic stress higher self-harm behavior psychosis-like experiences4. As predicted basis evidence day-time synchronizer clock mammals, success bright therapy during day lower disorders4. Triangulation animal models, experimental humans, epidemiology provided strong role daily good health. A possible causative etiology pathophysiology least may surprise those who think these epiphenomena accompany most disorders. However, recent discoveries regarding regulation many physiologic behavioral parameters system2, 3, alongside developments longitudinal epidemiology5, challenged assumption. Indeed, it strongly established across clinical, laboratory field-based settings related SCRD-relevant features, stable trait-like profiles delayed phase, long time, preference eveningness2, 3; melatonin body temperature rhythms; abnormal time relationships between phase markers cycle6. Accumulating suggests dysregulation likely be cross-diagnostic rather than disorder-specific3, especially key affective instability), impulsivity), cognitive disinhibition), immune-metabolic insulin resistance, raised C-reactive protein blood levels) phenotypes2. Empirical advances predictive significance prior first episode evident domain. SCRD-related factors eveningness social rhythms observed at-risk offspring parent disorder) youth meta-analytic prospective pre-existing SCRD 40% onset disorder7. study 2,000 adolescents young seeking help early-intervention clinics found disturbance transition earlier later stage disorders8. Studies focusing intensive measurement within- between-day dynamics motor activity appear dysregulated cross-reactive control populations highlighted need investigate biological interfaces systems, one candidate3. potentially important target personalized subgroup treatments selective serotonin reuptake inhibitors (SSRIs) increase sensitivity light, thereby destabilize individuals, concern9. requires urgent replication extension examination positive negative impacts exposures interventions, activation, restriction, stabilizers, antipsychotic agents, antidepressants. Some agents orexin antagonists, melatonin-based antidepressants) older pharmacotherapies lithium) do enhance stabilization systems models small patients disorders3. Further testing effects medications, potential treatment-relevant subtyping, highly warranted2, 9. There hurdles wider application insights. Accurate, real-time, repeated detection true timing internal its alignment external light-dark remains goal. Current measures largely limited either intensive, expensive, in-lab methods, indirect inferences wearable recordings sleep. Hence, clear development novel methods based gene expression, metabolic peripheral urinary markers. More sophisticated modelling techniques, tracking symptom clusters objective illness, then longitudinally, required unpick direction causation phenomena. Increased coordinated global investment timely, lead genuine therapeutic

Language: Английский

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Longitudinal Assessment of Seasonal Impacts and Depression Associations on Circadian Rhythm Using Multimodal Wearable Sensing: Retrospective Analysis

Journal of Medical Internet Research, Journal Year: 2024, Volume and Issue: 26, P. e55302 - e55302

Published: March 29, 2024

Background Previous mobile health (mHealth) studies have revealed significant links between depression and circadian rhythm features measured via wearables. However, the comprehensive impact of seasonal variations was not fully considered in these studies, potentially biasing interpretations real-world settings. Objective This study aims to explore associations severity wearable-measured rhythms while accounting for impacts. Methods Data were sourced from a large longitudinal mHealth study, wherein participants’ assessed biweekly using 8-item Patient Health Questionnaire (PHQ-8), behaviors, including sleep, step count, heart rate (HR), tracked Fitbit devices up 2 years. We extracted 12 14-day data preceding each PHQ-8 assessment, cosinor variables, such as HR peak timing (HR acrophase), nonparametric features, onset most active continuous 10-hour period (M10 onset). To investigate association also assessing impacts, we used three nested linear mixed-effects models feature: (1) incorporating score an independent variable, (2) adding seasonality, (3) interaction term season score. Results Analyzing 10,018 records alongside 543 participants (n=414, 76.2% female; median age 48, IQR 32-58 years), found that after adjusting effects, higher scores associated with reduced daily steps (β=–93.61, P<.001), increased sleep variability (β=0.96, delayed (ie, onset: β=0.55, P=.001; offset: β=1.12, P<.001; M10 β=0.73, P=.003; acrophase: β=0.71, P=.001). Notably, negative more pronounced spring (β × = –31.51, P=.002) summer –42.61, P<.001) compared winter. Additionally, correlation observed solely 1.06, P=.008). Moreover, winter, experienced shorter duration by 16.6 minutes, increase 394.5, delay 20.5 time 67.9 minutes during summer. Conclusions Our findings highlight influences on human their depression, underscoring importance considering research applications. indicates potential digital biomarkers depression.

Language: Английский

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The rhythm of mental health: the relationship of chronotype with psychiatric trait dimensions and diurnal variation in psychiatric symptoms

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 4, 2024

Abstract To advance the emergence of circadian-based therapies, this study characterized how psychiatric symptoms fluctuate across day and vary between individuals. Using a dimensional approach, we determined chronotype relates to 13 traits, modeled temporal development throughout using generalized additive mixed effects models. In preregistered study, subclinical sample completed trait scales scale at baseline ( N = 515, n 404 women, 109 men, 2 non-binary, M age 32.4 years, range 18–77), followed by 22 behaviors rated repeatedly ~08:00-00:00 410). Key findings are that 11 out traits were associated with being an evening-type, ranging from depression obsessive comulsive disorder, social anxiety, delusional ideation, while only mania was morning-type. Four distinct factors identified, each predicting worse symptom levels day. Fatigue-related exhibited strong time-of-day changes evening-types experiencing fatigue in morning morning-types evening. Evening-types had considerably lower drive motivation than early also more pronounced negative emotional ADHD-type evening, particularly among those high factors. These identified important research targets hold promise for improving mental health outcomes, such as strategies boost motivation. Furthermore, results emphasize relevance incorporating circadian factors, including chronotype, into translational interventions.

Language: Английский

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