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In the modern ‘24-h society,’ the sleep–wake cycle is progressively losing its close association with the dark/light alternation as work and leisure activities have progressively spread to the whole day and colonized the night hours. This causes interferences on circadian rhythms and sleep length and quality, which may have negative short- and long-term effects on performance efficiency, health, and well-being, with consequent high costs for individuals, companies, and the whole society. Several personal, organizational, and social factors interact in modulating the extent and severity of such impact on human life.

This case study reports the potential effectiveness of outpatient virtual dark therapy self-treatment for Bipolar I disorder. The patient desired side-effect free, nonallopathic outpatient treatment for Bipolar I Disorder. The patient was diagnosed Bipolar I, which was mild, and was recently manic. Previous interventions included medication, routine, exercise, and early symptom recognition. In this study, virtual dark therapy was added using Amber Lenses (AL). The outcome of this study was a reduction in symptoms and termination of medication. Though novel, this preliminary case study suggests that more research on virtual dark therapy in Bipolar disorder is warranted, including additional case studies as a precursor to randomized controlled trials.

This review will aim to scope the literature to discover and synthesise the prevalence of investigations of different types of chronotherapies across a variety of groups and populations, with specific attention paid to the therapeutic effectiveness of these interventions on mood. It will also identify gaps and areas of depth in the literature to inform future research activity in this area. A secondary aim of the review will take advantage of the hypothesis-generating nature of scoping reviews to (a) explore evidence for the putative mechanistic underpinnings of chronobiological interventions and (b) develop hypotheses about treatment components in existing interventions that warrant inclusion in a future evidence-informed, multi-faceted, chronobiological intervention.

Along with many physiological alterations in normal aging, sleep patterns change with aging, independent of other factors such as medical comorbidity and medications. Age-related changes in sleep include advanced sleep timing, shortened nocturnal sleep duration, increased frequency of daytime naps, increased number of nocturnal awakenings and time spent awake during the night, decreased slow wave sleep, and other changes. Most of these changes appear to occur between young and middle adulthood, as sleep parameters remain largely unchanged among healthy older adults. In addition, the circadian system and sleep homeostatic mechanisms become less robust with normal aging. In addition, the amount and pattern of sleep-related hormone secretion change in normal aging. All these changes contribute to or correlate with age-related changes in sleep. However, healthy older adults are less likely to report sleep problems. Finally, the causes of sleep disturbances in older adults are multifactorial, which include medical and psychiatric conditions, primary sleep disorders, and changes in environment, social engagement, and lifestyle.

Blue-blocking glasses, also known as amber glasses, are plastic glasses that primarily block blue light. Blue-blocking glasses have been studied as a sleep intervention for insomnia, delayed sleep-phase disorder, shift work, jet lag, and nonpathologic sleep improvement. Blue-blocking glasses have also been studied as a treatment for bipolar disorder, major depression, and postpartum depression. Blue-blocking glasses improve sleep by inducing dim-light melatonin onset by reducing activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) which are most sensitive to blue light and are a major input for circadian regulation; their mechanism for mood regulation is unclear but may be similar to that of dark therapy for bipolar disorder where patients are kept in darkness for an extended period every night. A systematic search of the scientific literature identified a total of 29 experimental publications involving evening wear of blue-blocking glasses for sleep or mood disorders. These consisted of 16 randomized controlled trials (RCTs) published in journals with a total of 453 patients, 5 uncontrolled trials, 1 case series, 1 case study, and 6 abstracts from conference proceedings. Only 1 case study and 1 RCT were for acutely manic patients but both found substantial decreases in manic symptoms with the use of blue-blocking glasses; these give preliminary clinical evidence of efficacy that makes blue-blocking glasses a high-yield intervention to study for bipolar disorder. Findings in the 3 publications for major depression and postpartum depression were heterogeneous and conflicting as to their efficacy. Out of the 24 publications focusing on sleep, there was substantial evidence for blue-blocking glasses being a successful intervention for reducing sleep onset latency in patients with sleep disorders, jet lag, or variable shift work schedules. Given the well-established biological mechanism and clinical research showing that blue-blocking glasses are effective for inducing sleep, they are a viable intervention to recommend to patients with insomnia or a delayed sleep phase.

Sleep problems and circadian misalignment affect health and well-being and are highly prevalent in those with co-morbid neuropsychiatric disorders. Interventions altering light exposure patterns of affected individuals are a promising non-pharmacological treatment option, shown by previous meta-analyses to improve sleep, and often described as minimally invasive. To best translate laboratory-based mechanistic research into effective treatments, acceptability and barriers to adherence should be understood, but these have not yet been systematically evaluated. Here, we examined evidence regarding adherence and acceptability in studies of light or dark interventions using various delivery devices and protocols to improve sleep in intrinsic circadian rhythm sleep–wake disorders and neuropsychiatric illness. Attrition during intervention was low, and reported experiences were largely positive, but measurement and reporting of self-reported experiences, expectations, and adverse effects were poor. Approaches to management and measurement of adherence were varied, and available light monitoring technology appeared under-exploited, as did mobile technology to prompt or track adherence. Based on these findings we suggest recommended reporting items on acceptability and adherence for future investigations. Few studies assessed baseline light exposure patterns, and few personalised interventions. Overall, many applied studies exhibited an approach to light schedule interventions still reminiscent of laboratory protocols; this is unlikely to maximise acceptability and clinical effectiveness. For the next phase of translational research, user acceptability and adherence should receive increased attention during intervention design and study design. We suggest framing light therapies as complex interventions, and emphasise the occupationally embedded (daily activity routine embedded) context in which they occur.

SUMMARYLight is the most important environmental influence (zeitgeber) on the synchronization of the circadian system in humans. Excess light exposure during the evening and night-time affects secretion of the hormone melatonin, which in turn modifies the temporal organization of circadian rhythms, including the sleep–wake cycle. As sleep disturbances are prominent in critically ill medical and psychiatric patients, researchers began to examine the impact of light exposure on clinical outcomes and length of hospitalization. In psychiatric inpatients, exposure to bright morning light or use of blue blocking glasses have proved useful interventions for mood disorders. Recently, knowledge about light and the circadian system has been applied to the design of inpatient facilities with dynamic lighting systems that change according to time of day. The installation of ‘circadian lighting’ alongside technologies for monitoring sleep–wake patterns could prove to be one of the most practical and beneficial innovations in inpatient psychiatric care for more than half a century.

Introduction Symptoms of postpartum insomnia are common however interventions remain scarce. Cognitive Behavioural Therapy (CBT) and Light Dark Therapy (LDT) target distinct mechanisms to improve sleep. This randomised controlled superiority trial compared CBT and LDT against treatment-as-usual (TAU) in reducing maternal postpartum insomnia symptoms. Methods Nulliparous females 4–12 months postpartum with self-reported symptoms of insomnia (Insomnia Severity Index scores >7) were included; excluded were those at risk or with high medical/psychiatric needs. Eligible participants were randomised 1:1:1 to 6 weeks of CBT, LDT (gaining light upon awakening, night-time light avoidance) or TAU. Interventions were therapist-assisted through two telephone calls and included automated self-help emails over six weeks. Symptoms of insomnia (ISI; primary outcome), sleep disturbance, fatigue, sleepiness, depression, and anxiety were assessed at baseline, mid-intervention, post-intervention, and 1-month post-intervention. Latent growth models were used. Results 114 participants (mean age=32.2±4.6 years) were randomised. There were significantly greater reductions in insomnia and sleep disturbance in both intervention groups with very large effect sizes (d>1·4, p0.08). Conclusion Therapist-assisted CBT and LDT are both efficacious for reducing postpartum insomnia symptoms. Findings were mixed for fatigue, sleepiness and mood. Future research is needed on predictors of treatment response.

Background: Symptoms of insomnia are common in new mothers and have been associated with a range of negative maternal and child outcomes. Despite this, interventions to improve maternal postpartum sleep remain scarce. Cognitive Behavioural Therapy (CBT) and Light Dark Therapy (LDT) represent two promising interventions for insomnia symptoms and associated daytime consequences such as fatigue. This randomised controlled trial examines whether CBT and LDT improve maternal insomnia symptoms as the primary outcome and maternal sleep disturbance, mood, fatigue, and sleepiness as secondary outcomes. This protocol paper outlines the development, design, and implementation of the trial.Methods: Participants are an Australian community-sample of 90 first-time mothers who are 4–12 months postpartum with self-reported symptoms of insomnia (Insomnia Severity Index scores ≥ 8). Exclusion criteria include current severe sleep/psychiatric disorders, unsettled infant sleep behaviour, sleep-affecting medication use, and photosensitivity. Eligible women are randomised into a CBT (strategies targeting sleep, worries, fatigue, and relaxation), LDT, or a treatment-as-usual control condition. Interventions are therapist-assisted and personalised through two telephone calls and include a series of automated intervention emails delivered over 6 weeks. Primary and secondary outcomes are assessed at four time points: baseline, intervention mid-point, post-intervention, and 1-month post-intervention.Discussion: If found effective, these interventions could represent efficacious, safe, and inexpensive treatments for improving postpartum insomnia and mitigate its negative impact on maternal well-being. Interventions tested are highly scalable and can be integrated into postpartum care and made available to the broader community.ANZCTR trial registration: Accessible at: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12618000842268.

Altered behavioral rhythms are a fundamental diagnostic feature of mood disorders. Patients report worse subjective sleep and objective measures confirm this, implicating a role for circadian rhythm disruptions in mood disorder pathophysiology. Molecular clock gene mutations are associated with increased risk of mood disorder diagnosis and/or severity of symptoms, and mouse models of clock gene mutations have abnormal mood-related behaviors. The mechanism by which circadian rhythms contribute to mood disorders remains unknown, however, circadian rhythms regulate and are regulated by various biological systems that are abnormal in mood disorders and this interaction is theorized to be a key component of mood disorder pathophysiology. A growing body of evidence has begun defining how the interaction of circadian and neurotransmitter systems influences mood and behavior, including the role of current antidepressants and mood stabilizers. Additionally, the hypothalamus-pituitary-adrenal (HPA) axis interacts with both circadian and monoaminergic systems and may facilitate the contribution of environmental stressors to mood disorder pathophysiology. The central role of circadian rhythms in mood disorders has led to the development of chronotherapeutics, which are treatments designed specifically to target circadian rhythm regulators, such as sleep, light, and melatonin, to produce an antidepressant response.

Background: Insomnia symptoms are common during the postpartum period, yet interventions remain scarce. This trial aimed to simultaneously examine the efficacy of cognitive behavioural therapy (CBT) and light dark therapy (LDT), targeting different mechanisms, against treatment-as-usual (TAU), in reducing maternal postpartum insomnia symptoms. Methods: This three-arm randomised controlled trial recruited from the general community in Melbourne, Australia. Nulliparous females 4-12 months postpartum with self-reported insomnia symptoms (Insomnia Severity Index [ISI] scores >7) were included; severe medical/psychiatric conditions were excluded. Participants were randomised 1:1:1 to CBT, LDT, or TAU stratified by ISI (< or ≥14) and infant age (< or ≥8 months). Participants and principal investigators were unblinded. Six-week interventions were delivered via digital materials and telephone. The primary outcome was insomnia symptoms (ISI), assessed pre-, midpoint-, post- (primary endpoint), and one-month post-intervention. Analyses were intention-to-treat using latent growth models. Outcomes: Participants were recruited from 2018-09-07 to 2020-03-23. 114 participants (CBT=39, LDT=36, TAU=39; M age =32·20±4·62 years) were randomised (all included in analyses), 108 completed the intervention, one withdrew, and five did not respond to contact. There were significantly greater reductions in ISI scores in CBT and LDT (effect sizes -2·01 and -1·52 respectively, p 0·08). Four participants (11%) in the LDT group reported headaches, dizziness, or nausea; no others reported adverse events. Interpretation: Therapist-assisted CBT and LDT were safe, feasible, and efficacious in reducing postpartum insomnia symptoms. Clinical Trial Registration Details: The trial was registered prospectively with Australia and New Zealand Clinical Trials Registry (ACTRN12618000842268). Funding Information: Australian National Health and Medical Research Council, Department of Education RTP Scholarship. Lucimed SA supplied light therapy glasses. Declaration of Interests: Verma and Quin are recipients of Australian Government Research Training Program Scholarship; Bei (APP1140299) and Wiley (APP1178487) are supported by National Health and Medical Research Council Fellowships. Rajaratnam is the Chair of the Sleep Health Foundation (Australia) and separately received a payment from the Restorative Sleep Expert Panel (USD1000 paid to the University). Lucimed SA provided light therapy glasses free-of-cost for the duration of the trial; Lucimed SA had no input to the design and execution of the trial. Ethics Approval Statement: Ethics approval was obtained from the Monash University Human Research Ethics Committee (9780) and the Department of Education and Training Victoria (2018_003774). Informed consent was obtained from all participants.

Improvement of sleep is a central treatment goal for patients in a manic state. Blue‐blocking (BB) glasses as adjunctive treatment hasten overall recovery from mania. This method is an evolvement from dark therapy and builds on the discovery of the blue‐light‐sensitive retinal ganglion cell that signals daytime to the brain. We report effects of adjunctive BB glasses on actigraphy‐derived sleep parameters for manic inpatients as compared to placebo. Hospitalized patients with bipolar disorder in a manic state aged 18–70 years were recruited from five clinics in Norway from February 2012 to February 2015. The participants were randomly allocated to wearing BB glasses or placebo (clear glasses) as an adjunctive treatment from 18:00 to 08:00 hours for seven consecutive nights. Sleep and wake were monitored by actigraphy. From 32 eligible patients, 10 patients in each group qualified for the group analyses. The BB group's mean sleep efficiency was significantly higher at night 5 as compared to the placebo group (92.6% vs. 83.1%, p = .027). The 95% confidence interval (CI) was 89.4%–95.8% in the BB group and 75.9%–90.3% in the placebo group. There were fewer nights of interrupted sleep in the BB group: 29.6% versus 43.8% in the placebo group. The BB group received less‐intensive sleep‐promoting pharmacological treatment and showed significantly higher sleep efficiency and more consolidated sleep as compared to the placebo group. Our findings suggest sleep‐promoting effects through deactivating mechanisms. Adjunctive BB glasses seem to be useful for improving sleep for manic patients in the hospital setting. publishedVersion

The 24-h sleep-wake cycle is one of the most prominent outputs of the circadian clock system. At the same time, changes in sleep-wake behavior feedback on behavioral and physiological circadian rhythms, thus altering the coordination of the body's clock network. Sleep and circadian rhythm disruption have similar physiological endpoints including metabolic, cognitive, and immunologic impairments. This raises the question to which extent these phenomena are causally linked. In this review, we summarize different physiologic outcomes of sleep deprivation and mistimed sleep and discuss the experimental evidence for a mediating role of the circadian clock machinery in this context.

There is increasing evidence that sleep and circadian disruption can worsen the disease course in inflammatory bowel disease (IBD). Sleep and circadian disruption are prevalent in society and are associated with worse outcomes in IBD. Emerging research suggests sleep and circadian disruption can impact key components in IBD disease flares, including intestinal permeability, translocation of bacterial endotoxins, intestinal dysbiosis, and proinflammatory cytokines. Much of this research has been conducted in animal models. There is a clear need for large randomized controlled trials in human patients with IBD, where the potential for chronotherapeutic strategies to improve disease course can be tested.

Artificial light in modern society has led to the ubiquity of light exposure at night as individuals work night shifts and use light-emitting electronic devices before bedtime. These aberrant light conditions have detrimental consequences on cognitive and mental health, compelling the need to understand the mechanisms by which light affects brain functions. Although it was believed that aberrant light impairs health by first disrupting circadian rhythms and sleep, we showed that chronic exposure to a light cycle termed T7 (3.5 h of darkness, 3.5 h of light) caused mood and learning dysfunction in adult mice independent of sleep deprivation or circadian arrhythmicity, suggesting the direct effects of aberrant light on brain function. However, the mechanisms by which light directly causes mood and learning dysfunction remain poorly understood. In this study, we sought to determine whether exposure to the T7 cycle disrupts adult hippocampal neurogenesis, given that suppressed neurogenesis has been correlated with mood and learning dysfunction. After exposing adult mice to the T7 light cycle, we analyzed adult hippocampal neurogenesis by examining cellular proliferation and number of adult-born neurons. Contrary to our hypothesis that T7 would suppress neurogenesis, we found that adult mice exposed to 2 or 10 weeks of the T7 light cycle did not exhibit deficits in hippocampal neurogenesis. Our findings suggest that the direct effects of light on mood and learning do not depend on adult hippocampal neurogenesis.

While disturbances of the sleep-wake cycle are common in people with affective disorders, the characteristics of these disturbances differ greatly between individuals. This heterogeneity is likely to reflect multiple underlying pathophysiologies, with different perturbations in circadian systems contributing to the variation in sleep-wake cycle disturbances. Such disturbances may be particularly relevant in adolescents and young adults with affective disorders as circadian rhythms undergo considerable change during this key developmental period. This study aimed to identify profiles of sleep-wake disturbance in young people with affective disorders and investigate associations with biological circadian rhythms. Fifty young people with affective disorders and 19 control participants (aged 16-31 years) underwent actigraphy monitoring for approximately two weeks to derive sleep-wake cycle parameters, and completed an in-laboratory assessment including evening dim-light saliva collection for melatonin assay and overnight continuous core body temperature measurement. Cluster analysis based on sleep-wake cycle parameters identified three distinct patient groups, characterised by 'delayed sleep-wake', 'disrupted sleep', and 'long sleep' respectively. The 'delayed sleep-wake' group had both delayed melatonin onset and core temperature nadir; whereas the other two cluster groups did not differ from controls on these circadian markers. The three groups did not differ on clinical characteristics. These results provide evidence that only some types of sleep-wake disturbance in young people with affective disorders are associated with fundamental circadian perturbations. Consequently, interventions targeting endogenous circadian rhythms to promote a phase shift may be particularly relevant in youth with affective disorders presenting with delayed sleep-wake cycles.

Sleep and circadian rhythm disturbances are common in patients with neurodegenerative diseases such as Huntington's disease (HD). The aim of this study was to evaluate variability in circadian blood pressure (BP) to determine the association between abnormal circadian BP and sleep quality in patients with HD.Cross-sectional, multicenter study of 38 HD mutation carriers (23 premanifest and 15 early stage patients) who were compared to 38 age- and sex-matched controls. BP was evaluated by ambulatory blood pressure monitoring (ABPM). Based on the percentage decrease in nocturnal BP, subjects were classified as either dippers (≥10%) or non-dippers (10%). Sleep quality and daytime sleepiness were measured, respectively, using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Daytime Sleepiness Scale (ESS) and the scores on these indices were correlated with the ABPM findings.Sixty-three percent HD mutation carriers were non-dippers (86.7% of the symptomatic and 47.8% of the premanifest patients) versus 23.7% of controls (p = 0.001). In the HD group, sleep quality was significantly more impaired (PSQI5) (p = 0.016) with more excessive daytime sleepiness (ESS9) (p = 0.001) than in the control group. Nocturnal non-dipping was associated with worse sleep quality in patients (p = 0.011) but not in controls.These results show that patients with HD present early disturbances in the circadian rhythm of BP and that this altered nocturnal BP is associated with poor sleep quality. These findings suggest the potential role of subtle hypothalamic dysfunction in this population.

Fil: Zaki, Nevin F. W. Mansoura University. Faculty of Medicine. Department of Psychiatry; Egipto Fil: Spence, David Warren. Investigador independiente; Canadá Fil: BaHammam, Ahmed S. King Saud University. College of Medicine. University Sleep Disorders Center; Arabia Saudita Fil: Pandi Perumal, Seithikurippu R. Somnogen Inc; Estados Unidos Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Cardinali, Daniel Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina Fil: Brown, Gregory M. University of Toronto. Department of Psychiatry. Centre for Addiction and Mental Health; Canadá Abstract: Major depressive disorder (MDD) remains the most prevalent mental disorder and a leading cause of disability, affecting approximately 100 million adults worldwide. The disorder is characterized by a constellation of symptoms affecting mood, anxiety, neurochemical balance, sleep patterns, and circadian and/or seasonal rhythm entrainment. However, the mechanisms underlying the association between chronobiological parameters and depression remain unknown. A PubMed search was conducted to review articles from 1979 to the present, using the following search terms: "chronobiology," "mood," "sleep," and "circadian rhythms." We aimed to synthesize the literature investigating chronobiological theories of mood disorders. Current treatments primarily include tricyclic antidepressants and selective serotonin reuptake inhibitors, which are known to increase extracellular concentrations of monoamine neurotransmitters. However, these antidepressants do not treat the sleep disturbances or circadian and/or seasonal rhythm dysfunctions associated with depressive disorders. Several theories associating sleep and circadian rhythm disturbances with depression have been proposed. Current evidence supports the existence of associations between these, but the direction of causality remains elusive. Given the existence of chronobiological disturbances in depression and evidence regarding their treatment in improving depression, a chronobiological approach, including timely use of light and melatonin agonists, could complement the treatment of MDD.

Circadian rhythms influence our daily behavior. Individuals display preferences for activity at certain time of day and this circadian phenotype can be summarized with the concept of “chronotype” or circadian typology (CT). The chronotypes differ in the timing of many physiological and psychological variables. Individuals with an early circadian phase are morning-types (M-types), those with a delayed circadian phase are evening-types (E-types), and those with an intermediate circadian phase are neither-types (N-types). Nevertheless, the propensity toward morning or evening preferences can vary during the life. In particular, adolescence can represent a crucial time in which the sleep–wake cycle tends to become delayed. The circadian rhythm desynchronization is common in modern society and lead to negative health effects, not only for physical health, but also for cognitive and affective function. One of the most important variables that show a defined circadian rhythm is melatonin; human melatonin levels increase at night, but the acrophase of melatonin occurs earlier in M-type than in E-type. Aim of this review, after providing a description of the methods for detecting the CT, analyzes the propensity toward morning or evening preferences in different life periods and the interactions between melatonin and physiological functions associated to physical activity. Exercise, performed in morning or in evening sessions, can adjust circadian rhythm, supporting its application as a treatment for the circadian rhythm desynchronization, for example, resulting from jet lag or shift work. Interindividual differences should also be taken into account in case of changes of the circadian rhythms parameters of different variables that can influence health also in relation to sport.

The endogenous circadian rhythms are one of the cardinal processes that control sleep. They are self-sustaining biological rhythms with a periodicity of approximately 24 hours that may be entrained by external zeitgebers (German for time givers), such as light, exercise, and meal times. This article discusses the physiology of the circadian rhythms, their relationship to neurologic disease, and the presentation and treatment of circadian rhythm sleep-wake disorders.Classic examples of circadian rhythms include cortisol and melatonin secretion, body temperature, and urine volume. More recently, the impact of circadian rhythm on several neurologic disorders has been investigated, such as the timing of occurrence of epileptic seizures as well as neurobehavioral functioning in dementia. Further updates include a more in-depth understanding of the symptoms, consequences, and treatment of circadian sleep-wake disorders, which may occur because of extrinsic misalignment with clock time or because of intrinsic dysfunction of the brain. An example of extrinsic misalignment occurs with jet lag during transmeridian travel or with intrinsic circadian rhythm sleep-wake disorders such as advanced or delayed sleep-wake phase disorders. In advanced sleep-wake phase disorder, which is most common in elderly individuals, sleep onset and morning arousal are undesirably early, leading to impaired evening function with excessive sleepiness and sleep-maintenance insomnia with early morning awakening. By contrast, delayed sleep-wake phase disorder is characterized by an inability to initiate sleep before the early morning hours, with subsequent delayed rise time, leading to clinical symptoms of severe sleep-onset insomnia coupled with excessive daytime sleepiness in the morning hours, as patients are unable to "sleep in" to attain sufficient sleep quantity. Irregular sleep-wake rhythm disorder is misentrainment with patches of brief sleep and wakefulness spread throughout the day, leading to unstable sleep and waking behavioral patterns and an entirely idiosyncratic sleep-wake schedule.Familiarity with these major circadian rhythm sleep-wake disorder phenotypes and their overlap with other neurologic disorders is essential for the neurologist so that clinicians may intervene and improve patient functioning and quality of life.

Despite a complex relationship between mood, sleep and rhythm, the impact of circadian disruptions on bipolar disorder (BD) has not been clarified. The purpose of this systematic review was to define current evidence regarding chronotype and circadian rhythm patterns in BD patients. 42 studies were included, involving 3432 BD patients. Disruption of the biological rhythm was identified, even in drug-naïve BD patients and independently of mood status. Daily profiles of melatonin levels and cortisol indicated a delayed phase. Depression was more frequently associated with circadian alterations than euthymia. Few studies evaluated mania, demonstrating irregular rhythms. Evening type was more common in BD adults. Studies about the influence of chronotype on depressive symptoms showed conflicting results. Only one investigation observed the influences of chronotype in mania, revealing no significant association. Effects of psychoeducation and lithium on rhythm in BD patients were poorly studied, demonstrating no improvement of rhythm parameters. Studies about genetics are incipient. In conclusion, disruption in circadian rhythm and eveningness are common in BD. Prospective research evaluating the impact of circadian disruption on mood symptoms, metabolism, seasonality, the influence of age and the effects of mood stabilizers are needed.

The aim of this study was to assess complaints about sleep quality and to investigate circadian rhythms of melatonin secretion in peri- and postmenopausal women. Material and Methods: A total of 146 climacteric women were examined. All patients were divided into 2 groups: Group1 included 72 perimenopausal women and Group 2 included 74 postmenopausal women. Women were surveyed with special questionnaires: PSQI, FFS, ESS, Daytime Feeling and Functioning Scale. Insomnia Severity Index was calculated. Salivary melatonin content was determined (4 times a day) by immunoassay using Microplate Reader EL×808 (USA). Results: Perimenopausal women often complained about difficulties falling asleep (more than 20 minutes from the moment the light was turned off) and difficulties awakening in the morning, while postmenopausal women often complained about snoring and frequent awakenings during sleep(≥2 times). ISI was 21.3±0.54 in Group 1 and 24.8±0.31 in Group 2, which corresponded to insomnia. Daily melatonin secretion in perimenopausal patients with insomnia was altered – the maximal level was registered in the morning hours. The circadian rhythms of melatonin secretion in the group of postmenopausal women did not correlate to the occurrence of insomnia. Conclusion: We can recommend administration of melatonin in the evening time and light therapy in the early morning hours in the complex treatment of SDs in perimenopausal women for normalizing and shifting the chronobiological rhythms of melatonin secretion, and specific therapy is aimed to eliminate snoring for postmenopausal women.

Purpose of review Although several papers have described circadian regulation of the immune function, our goal is to address the reciprocal interactions between the circadian and immune systems.

This study aims to discuss possible reasons why research to date has not forged direct links between light at night, acute melatonin suppression or circadian disruption, and risks for disease.Data suggest that irregular light-dark patterns or light exposures at the wrong circadian time can lead to circadian disruption and disease risks. However, there remains an urgent need to: (1) specify light stimulus in terms of circadian rather than visual response; (2) when translating research from animals to humans, consider species-specific spectral and absolute sensitivities to light; (3) relate the characteristics of photometric measurement of light at night to the operational characteristics of the circadian system; and (4) examine how humans may be experiencing too little daytime light, not just too much light at night.To understand the health effects of light-induced circadian disruption, we need to measure and control light stimulus during the day and at night.

Light is the major synchronizer of circadian rhythms to local time on earth. Light can also elicit an acute alerting effect on humans. This paper discusses lighting characteristics that affect the circadian system and how self-luminous displays can be used to promote entrainment and alertness.

Exposure to Artificial Light At Night (ALAN) results in a disruption of the circadian system, which is deleterious to health. In industrialized countries, 75% of the total workforce is estimated to have been involved in shift work and night work. Epidemiologic studies, mainly of nurses, have revealed an association between sustained night work and a 50-100% higher incidence of breast cancer. The potential and multifactorial mechanisms of the effects include the suppression of melatonin secretion by ALAN, sleep deprivation, and circadian disruption. Shift and/or night work generally decreases the time spent sleeping, and it disrupts the circadian time structure. In the long run, this desynchronization is detrimental to health, as underscored by a large number of epidemiological studies that have uncovered elevated rates of several diseases, including cancer, diabetes, cardiovascular risks, obesity, mood disorders and age-related macular degeneration. It amounts to a public health issue in the light of the very substantial number of individuals involved. The IARC has classified shift work in group 2A of "probable carcinogens to humans" since "they involve a circadian disorganization". Countermeasures to the effects of ALAN, such as melatonin, bright light, or psychotropic drugs, have been proposed as a means to combat circadian clock disruption and improve adaptation to shift and night work. We review the evidence for the ALAN impacts on health. Furthermore, we highlight the importance of an in-depth mechanistic understanding to combat the detrimental properties of exposure to ALAN and develop strategies of prevention.

Non-24-h sleep-wake disorder (non-24) is a circadian rhythm disorder occurring in 55-70% of totally blind individuals (those lacking conscious light perception) in which the 24-h biological clock (central, hypothalamic, circadian pacemaker) is no longer synchronized, or entrained, to the 24-h day. Instead, the overt rhythms controlled by the biological clock gradually shift progressively earlier or later (free run) in accordance with the clock's near-24-h period, resulting in a recurrent pattern of daytime hypersomnolence and night-time insomnia. Orally administered melatonin and the melatonin agonist tasimelteon have been shown to entrain (synchronize) the circadian clock, resulting in improvements in night-time sleep and daytime alertness. We review the basic principles of circadian rhythms necessary to understand and treat non-24. The time of melatonin or tasimelteon administration must be considered carefully. For most individuals, those with circadian periods longer than 24 h, low-dose melatonin should be administered about 6 h before the desired bedtime, while in a minority, those with circadian periods shorter than 24 h (more commonly female individuals and African-Americans), melatonin should be administered at the desired wake time. Small doses (e.g., 0.5 mg of melatonin) that are not soporific would thus be preferable. Administration of melatonin or tasimelteon at bedtime will entrain individuals with non-24 but at an abnormally late time, resulting in continued problems with sleep and alertness. To date, tasimelteon has only been administered 1 h before the target bedtime in patients with non-24. Issues of cost, dose accuracy, and purity may figure into the decision of whether tasimelteon or melatonin is chosen to treat non-24. However, there are no head-to-head studies comparing efficacy, and studies to date show comparable rates of treatment success (entrainment).

Objective/Background Delayed sleep–wake phase disorder (DSWPD) is associated with a delayed timing of circadian rhythms, and this delay is suggested to be the basis of the disorder. However, this has been questioned due to frequent relapses following treatment based on this aetiology. Recent studies have emerged suggesting personality factors may contribute to sleep patterns in DSWPD. The aim of this study was to further investigate circadian and personality factors in DSWPD patients as well as patients with non-24-h sleep–wake rhythm disorder (N24SWD) relative to control sleepers. Patients/Methods This sample consisted of 16 DSWPD (age = 21.1 ± 2.8, 10 m, 7 f), and three N24SWD patients (age = 24.0 ± 4.4, 2 m, 1 f). Controls were seven males and seven females (age = 23.4 ± 5.9). Before starting an 80-h modified constant routine, eligible participants' sleep patterns were monitored for a week and they completed a personality questionnaire (NEO PI–R). An ultradian routine with alternating 20-min sleep opportunities and 40 min of enforced wakefulness was used to measure the timing of endogenous circadian temperature and melatonin rhythms. Results As compared with controls, DSWPD patients reported higher neuroticism, significantly lower extraversion, conscientiousness and agreeableness. Similarly, N24SWD patients' patterns of personality traits were similar to that of DSWPD. Conscientiousness, in particular, was associated with phase timings of circadian rhythms as well as sleep measures and lifestyle factors within the DSWPD group. Conclusions These findings suggest that circadian rhythm sleep–wake disorders (CRSWDs) may not only stem from circadian abnormalities but personality factors may also drive lifestyle choices, including sleep timing.

Summary Splitting of the behavioural activity phase has been found in nocturnal rodents with suprachiasmatic nucleus (SCN) coupling disorder. A similar phenomenon was observed in the sleep phase in the diurnal human discussed here, suggesting that there are so-called evening and morning oscillators in the SCN of humans. The present case suffered from bipolar disorder refractory to various treatments, and various circadian rhythm sleep disorders, such as delayed sleep phase, polyphasic sleep, separation of the sleep bout resembling splitting and circabidian rhythm (48 h), were found during prolonged depressive episodes with hypersomnia. Separation of sleep into evening and morning components and delayed sleep-offset (24.69-h cycle) developed when lowering and stopping the dose of aripiprazole (APZ). However, resumption of APZ improved these symptoms in 2 weeks, accompanied by improvement in the patient's depressive state. Administration of APZ may improve various circadian rhythm sleep disorders, as well as improve and prevent manic–depressive episodes, via augmentation of coupling in the SCN network.

Reports of sleep disturbances in attention deficit hyperactivity disorder (ADHD) are common in both children and adults; however, the aetiology of such disturbances is poorly understood. One potentially important mechanism which may be implicated in disrupted sleep in ADHD is the circadian clock, a known key regulator of the sleep/wake cycle. In this systematic review, we analyse the evidence for circadian rhythm changes associated with ADHD, as well as assessing evidence for therapeutic approaches involving the circadian clock in ADHD. We identify 62 relevant studies involving a total of 4462 ADHD patients. We find consistent evidence indicating that ADHD is associated with more eveningness/later chronotype and with phase delay of circadian phase markers such as dim light melatonin onset and delayed sleep onset. We find that there is evidence that melatonin treatment may be efficacious in addressing ADHD-related sleep problems, although there are few studies to date addressing other chronotherapeutic approaches in ADHD. There are only a small number of genetic association studies which report linkages between polymorphisms in circadian clock genes and ADHD symptoms. In conclusion, we find that there is consistent evidence for circadian rhythm disruption in ADHD and that such disruption may present a therapeutic target that future ADHD research might concentrate explicitly on.

Rhythmicity of physiological parameters is found in virtually all living systems. The circadian rhythm with its most obvious expression, the sleep–wake cycle, is closely tied to the diurnal rhythm of day and night. A disturbance of this highly regulated system can lead to circadian misalignment resulting in sleeping difficulties with consequences on many physiological functions like psychological and physical performance, the metabolism, and the immune system as it could be found in night shift workers or in people suffering from chronic jet lag. Stress in its many forms, generally perceived as an excessive demand on human psychological and/or physiological adaptive capabilities, can have a direct influence on the human sleeping pattern due to the integration of neuronal and hormonal pathways of the stress reaction and the circadian regulation. Thus excessive and/or chronic stress can lead to a disturbance of the circadian rhythm as it can be found in diseases like depression and posttraumatic stress disorder. Extreme environments such as high altitude, hot or cold environments, or microgravity also can alter human sleep patterns as well as during isolation and confinement – experimental setups that serve to simulate the isolated nature of long-term space travel.

Aims To systematically review the literature on the efficacy and tolerability of the major chronotherapeutic treatments of bipolar disorders (BD)-bright light therapy (LT), dark therapy (DT), treatments utilizing sleep deprivation (SD), melatonergic agonists (MA), interpersonal social rhythm therapy (IPSRT), and cognitive behavioral therapy adapted for BD (CBTI-BP)-and propose treatment recommendations based on a synthesis of the evidence. Methods PRISMA-based systematic review of the literature. Results The acute antidepressant (AD) efficacy of LT was supported by several open-label studies, three randomized controlled trials (RCTs), and one pseudorandomized controlled trial. SD showed rapid, acute AD response rates of 43.9%, 59.3%, and 59.4% in eight case series, 11 uncontrolled, studies, and one RCT, respectively. Adjunctive DT obtained significant, rapid anti-manic results in one RCT and one controlled study. The seven studies on MA yielded very limited data on acute antidepressant activity, conflicting evidence of both antimanic and maintenance efficacy, and support from two case series of improved sleep in both acute and euthymic states. IPSRT monotherapy for bipolar II depression had acute response rates of 41%, 67%, and 67.4% in two open studies and one RCT, respectively; as adjunctive therapy for bipolar depression in one RCT, and efficacy in reducing relapse in two RCTs. Among euthymic BD subjects with insomnia, a single RCT found CBTI-BP effective in delaying manic relapse and improving sleep. Chronotherapies were generally safe and well-tolerated. Conclusions The outcome literature on the adjunctive use of chronotherapeutic treatments for BP is variable, with evidence bases that differ in size, study quality, level of evidence, and non-standardized treatment protocols. Evidence-informed practice recommendations are offered.

Introduction Symptoms of insomnia are common in the postpartum period and are associated with a range of negative outcomes. Despite this, interventions to improve maternal postpartum sleep remain scarce. Cognitive Behavioral Therapy (CBT) and Light Dark Therapy (LDT) target two different mechanisms to reduce sleep disturbance. This randomized controlled trial examined the efficacy of CBT and LDT against a treatment-as-usual (TAU) condition in reducing maternal postpartum insomnia symptoms. Methods Nulliparous women 4–12 months postpartum with self-reported symptoms of insomnia (Insomnia Severity Index scores [ISI] >7) were included; excluded were those with: current severe health/psychiatric conditions, unsettled infant behaviors, sleep-affecting medication use and photosensitivity. Eligible women were randomized 1:1:1 to 6 weeks of CBT (CBT for insomnia and fatigue), LDT (morning bright light therapy, evening light hygiene), or TAU. Interventions were therapist-assisted and personalized through two telephone calls and included automated self-help intervention materials (i.e., emails) delivered over six weeks. Symptoms of insomnia (ISI; primary outcome), fatigue, sleepiness, depression, and anxiety were assessed at baseline, mid-intervention, post-intervention, and 1-month post-intervention. Analyses were intention-to-treat latent growth models. Results 114 women were randomized (mean age = 32.20 ± 4.62 years) and 108 women completed the intervention. Compared to TAU, symptoms of insomnia significantly reduced from baseline to post-intervention in both CBT and LDT groups (p-values 1.5) at post-intervention; gains were maintained at follow-up. Fatigue symptoms significantly reduced in the CBT group (p 0.08). Conclusion Therapist-assisted self-help CBT and LDT with different therapeutic mechanisms are both efficacious for reducing maternal insomnia symptoms during the postpartum period. Findings were mixed for fatigue, sleepiness and mood. Future research on predictors of treatment responses is needed. Support (if any) Australian National Health and Medical Research Council, Department of Education RTP Scholarship. Lucimed SA supplied light therapy glasses. Funders had no role in design/implementation of the trial. ANZCTR: ACTRN12618000842268.

Affective disorders in young people have been associated with disruptions in circadian rhythms, including abnormalities in secretion of the pineal hormone melatonin. Previous research reports relationships between pineal gland volumes, melatonin secretion, and sleep-wake cycles, but the relationship between these factors has not been explored in affective disorders. This study aimed to characterize these factors and explore associations with mood symptoms and functioning in a sample of young people with affective disorders. Pineal volume from magnetic resonance imaging and melatonin assay from evening dim-light saliva collection were evaluated in 50 individuals (15-30 years old; 72 % female) with bipolar, depressive, or anxiety disorders. Actigraphy monitoring was also conducted for approximately two weeks to derive sleep-wake measures. Pineal volume was associated with melatonin secretion across the evening, replicating previous findings in psychiatrically healthy individuals. Pineal volume was smaller in participants in which melatonin onset was not detected. Timing of melatonin secretion was related to sleep timing, but amount of melatonin and pineal volume were not related to any sleep-wake measures. A shorter phase angle between onset of melatonin secretion and sleep onset was associated with longer total sleep time. Lower melatonin levels were associated with poorer social and occupational functioning. Although pineal volume is not directly related to sleep disturbances or symptoms, melatonin may influence both sleep-wake cycles and functioning in the early stages of affective disorder. Causal links remain to be established, however, treatments that target circadian rhythms may be useful in improving functioning in young people with affective disorders.

Sleep disturbances are common in psychiatric disorders, but the causal relationship between the two and the underlying genetic factors is unclear. The DISC1 gene is strongly linked to mood disorders and schizophrenia in a Scottish pedigree. In an earlier study we found a sleep homeostasis disturbance in a Drosophila model overexpressing wild-type human DISC1. Here we aimed to explore the relationship between sleep and the DISC1 gene in a mammalian model, a novel transgenic mouse model expressing full-length human DISC1. We assessed circadian rhythms by monitoring wheel running activity under normal 24-h light:dark conditions and in constant darkness and found the DISC1 mice to have normal circadian photoentrainment and normal intrinsic circadian period. We also assessed sleep duration and quality in the DISC1 mice and found that they were awake longer than wild-type controls at baseline with a tendency for lower rebound of delta activity during recovery from a short sleep deprivation. Thus we suggest that DISC1 may be involved in sleep regulation.

Preclinical Research Most neuropsychiatric research, including that related to the circadian system, is performed using nocturnal animals, mainly laboratory mice and rats. Mood disorders are known to be associated with circadian rhythm abnormalities, but the mechanisms by which circadian rhythm disruptions interact with depression remain unclear. As the circadian system of diurnal and nocturnal mammals differs, we previously suggested that the utilization of diurnal animal models may be advantageous for understanding these relations. During the last 10 years, we and others established the validity of several diurnal rodent species as a model for the interactions between circadian rhythms and depression. Diurnal rodents respond to photoperiod manipulation in a similar way to humans, the behavioral outcome is directly related to the circadian system, and treatment that is effective in patients is also effective in the model. Moreover, less effective treatments in patients are also less effective in the model. We, therefore, suggest that using diurnal animal models to study circadian rhythms-related affective disorders, such as depression, will provide new insights that will hopefully lead to the development of more effective treatments. Drug Dev Res 77 : 347-356, 2016. © 2016 Wiley Periodicals, Inc.