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Using data from 1721 participants in a community-based randomized control trial of digital cognitive behavioural therapy for insomnia compared with patient education, we employed linear mixed modelling analyses to examine whether chronotype moderated the benefits of digital cognitive behavioural therapy for insomnia on self-reported levels of insomnia severity, fatigue and psychological distress. Baseline self-ratings on the reduced version of the Horne-Östberg Morningness-Eveningness Questionnaire were used to categorize the sample into three chronotypes: morning type (n = 345; 20%); intermediate type (n = 843; 49%); and evening type (n = 524; 30%). Insomnia Severity Index, Chalder Fatigue Questionnaire, and Hospital Anxiety and Depression Scale were assessed pre- and post-intervention (9 weeks). For individuals with self-reported morning or intermediate chronotypes, digital cognitive behavioural therapy for insomnia was superior to patient education on all ratings (Insomnia Severity Index, Chalder Fatigue Questionnaire, and Hospital Anxiety and Depression Scale) at follow-up (p-values ≤ 0.05). For individuals with self-reported evening chronotype, digital cognitive behavioural therapy for insomnia was superior to patient education for Insomnia Severity Index and Chalder Fatigue Questionnaire, but not on the Hospital Anxiety and Depression Scale (p = 0.139). There were significant differences in the treatment effects between the three chronotypes on the Insomnia Severity Index (p = 0.023) estimated difference between evening and morning type of -1.70, 95% confidence interval: -2.96 to -0.45, p = 0.008, and estimated difference between evening and intermediate type -1.53, 95% confidence interval: -3.04 to -0.03, p = 0.046. There were no significant differences in the treatment effects between the three chronotypes on the Chalder Fatigue Questionnaire (p = 0.488) or the Hospital Anxiety and Depression Scale (p = 0.536). We conclude that self-reported chronotype moderates the effects of digital cognitive behavioural therapy for insomnia on insomnia severity, but not on psychological distress or fatigue.

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

Sleep and circadian rhythms disturbances (SCRD) in young people at high risk or with early onset of bipolar disorders (BD) are poorly understood. We systematically searched for studies of self, observer or objective estimates of SCRD in asymptomatic or symptomatic offspring of parents with BD (OSBD), individuals with presentations meeting recognised BD-at-risk criteria (BAR) and youth with recent onset of full-threshold BD (FT-BD). Of 76 studies eligible for systematic review, 35 (46%) were included in random effects meta-analyses. Pooled analyses of self-ratings related to circadian rhythms demonstrated greater preference for eveningness and more dysregulation of social rhythms in BAR and FT-BD groups; analyses of actigraphy provided some support for these findings. Meta-analysis of prospective studies showed that pre-existing SCRD were associated with a 40% increased risk of onset of BD, but heterogeneity in assessments was a significant concern. Overall, we identified longer total sleep time (Hedges g: 0.34; 95% confidence intervals:.1, .57), especially in OSBD and FT-BD and meta-regression analysis indicated the effect sizes was moderated by the proportion of any sample manifesting psychopathology or receiving psychotropic medications. This evolving field of research would benefit from greater attention to circadian rhythm as well as sleep quality measures.

INTRODUCTION: Insomnia is highly prevalent in outpatients receiving treatment for mental disorders. Cognitive-behavioural therapy for insomnia (CBT-I) is a recommended first-line intervention. However, access is limited and most patients with insomnia who are receiving mental healthcare services are treated using medication. This multicentre randomised controlled trial (RCT) examines additional benefits of a digital adaptation of CBT-I (dCBT-I), compared with an online control intervention of patient education about insomnia (PE), in individuals referred to secondary mental health clinics. METHODS AND ANALYSIS: A parallel group, superiority RCT with a target sample of 800 participants recruited from treatment waiting lists at Norwegian psychiatric services. Individuals awaiting treatment will receive an invitation to the RCT, with potential participants undertaking online screening and consent procedures. Eligible outpatients will be randomised to dCBT-I or PE in a 1:1 ratio. Assessments will be performed at baseline, 9 weeks after completion of baseline assessments (post-intervention assessment), 33 weeks after baseline (6 months after the post-intervention assessment) and 61 weeks after baseline (12 months after the post-intervention assessment). The primary outcome is between-group difference in insomnia severity 9 weeks after baseline. Secondary outcomes include between-group differences in levels of psychopathology, and measures of health and functioning 9 weeks after baseline. Additionally, we will test between-group differences at 6-month and 12-month follow-up, and examine any negative effects of the intervention, any changes in mental health resource use, and/or in functioning and prescription of medications across the duration of the study. Other exploratory analyses are planned. ETHICS AND DISSEMINATION: The study protocol has been approved by the Regional Committee for Medical and Health Research Ethics in Norway (Ref: 125068). Findings from the RCT will be disseminated via peer-reviewed publications, conference presentations, and advocacy and stakeholder groups. Exploratory analyses, including potential mediators and moderators, will be reported separately from main outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04621643); Pre-results.

Summary In bipolar disorders, abnormalities of sleep patterns and of circadian rhythms of activity are observed during mood episodes, but also persist during euthymia. Shared vulnerabilities between mood disorders and abnormalities of sleep patterns and circadian rhythms of activity have been suggested. This exploratory study investigated the association between polygenic risk scores for bipolar disorder and major depressive disorder, actigraphy estimates of sleep patterns, and circadian rhythms of activity in a sample of 62 euthymic individuals with bipolar disorder. The polygenic risk score – bipolar disorder and polygenic risk score – major depressive disorder were calculated for three stringent thresholds of significance. Data reduction was applied to aggregate actigraphy measures into dimensions using principal component analysis. A higher polygenic risk score – major depressive disorder was associated with more fragmented sleep, while a higher polygenic risk score – bipolar disorder was associated with a later peak of circadian rhythms of activity. These results remained significant after adjustment for age, sex, bipolar disorder subtype, body mass index, current depressive symptoms, current tobacco use, and medications prescribed at inclusion, but not after correction for multiple testing. In conclusion, the genetic vulnerabilities to major depression and to bipolar disorder might be associated with different abnormalities of sleep patterns and circadian rhythms of activity. The results should be replicated in larger and independent samples. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Insomnia is a major public health concern. While cognitive behaviour therapy for insomnia (CBT-I) is acknowledged as the best available intervention, there are unanswered questions about its wider dissemination, socioeconomic benefits and its impact on health resource utilisation. The aim of this randomised controlled trial (RCT) is to investigate the effectiveness of a fully automated online version of CBT-I compared with online patient education about sleep (PE). Outcome measures comprise changes in symptoms of insomnia, time off work due to sick leave as well as medication and health resource utilisation. Also, we will examine (i) putative mediators of the effects of CBT-I on insomnia severity and (ii) selected potential psycho-bio-social moderators of the effects of the interventions. METHODS AND ANALYSIS: A parallel-group RCT will be conducted in a target sample of about 1500 adults recruited across Norway. Participants will complete an online screening and consent process. Those who meet eligibility criteria will be randomised to receive direct access to fully automated online CBT-I or to an online PE programme. The primary outcome is change in insomnia severity immediately postintervention; secondary outcomes are change in daytime functioning and other sleep measures postintervention and at 6-month and 24-month follow-up. Objective data from national registries will be obtained at two time points (1 year and 2 years post-treatment), allowing a mirror image study of preintervention and postintervention rates of sick leave, and of medication and healthcare utilisation by condition. ETHICS AND DISSEMINATION: The study protocol was approved by the Regional Committee for Medical and Health Research Ethics in South East Norway (2015/134). Findings from the RCT will be disseminated in peer-reviewed publications and conference presentations. Exploratory analyses of potential mediators and moderators will be reported separately. User-friendly outputs will be disseminated to patient advocacy and other relevant organisations. TRIAL REGISTRATION NUMBER: NCT02558647; Pre-results.

Aim: To examine whether polygenic risk scores (PRS) for neuroticism, depression, bipolar disorder and schizophrenia are higher in individuals manifesting trans‐diagnostic risk factors for the development of major mental disorders and whether PRS enhance prediction of early onset full‐threshold disorders. Methods: Using data from the Brisbane Longitudinal Twin Study, we examined individual PRS for neuroticism, depression, bipolar disorder and schizophrenia, recorded evidence of subthreshold syndromes and family history of mood and/or psychotic disorders and noted progression to trans‐diagnostic clinical caseness (onset of major mental disorders) at follow‐up. We undertook multivariate, receiver operating curve and logistic regression analyses that were adjusted for known variables of influence (age, twin status, and so on). Results: Of 1473 eligible participants (female = 866, 59%; mean age 26.3 years), 28% (n = 409) met caseness criteria for a mood and/or psychotic disorder. All PRS were higher in cases versus non‐cases but associations with different levels of risk were inconsistent. The prediction of caseness (reported as area under the curve with 95% confidence intervals [CI]) improved from 0.68 (95% CI: 0.65, 0.71) when estimated using clinical risk factors alone up to 0.71 (95% CI: 0.69, 0.73) when PRS were added to the model. Logistic regression identified five variables that optimally classified individuals according to caseness: age, sex, individual risk characteristics, PRS for depression and mental health case status of cotwins or siblings. Conclusions: The findings need replication. However, this exploratory study suggests that combining PRS with other risk factors has the potential to improve outcome prediction in youth. [ABSTRACT FROM AUTHOR]

Depression, schizophrenia, and bipolar disorder are three of the four most burdensome problems in people aged under 25 years. In psychosis and depression, psychological interventions are effective, low-risk, and high-benefit approaches for patients at high risk of first-episode or early-onset disorders. We review the use of psychological interventions for early-stage bipolar disorder in patients aged 15-25 years. Because previous systematic reviews had struggled to identify information about this emerging sphere of research, we used evidence mapping to help us identify the extent, distribution, and methodological quality of evidence because the gold standard approaches were only slightly informative or appropriate. This strategy identified 29 studies in three target groups: ten studies in populations at high risk for bipolar disorder, five studies in patients with a first episode, and 14 studies in patients with early-onset bipolar disorder. Of the 20 completed studies, eight studies were randomised trials, but only two had sample sizes of more than 100 individuals. The main interventions used were family, cognitive behavioural, and interpersonal therapies. Only behavioural family therapies were tested across all of our three target groups. Although the available interventions were well adapted to the level of maturity and social environment of young people, few interventions target specific developmental psychological or physiological processes (eg, ruminative response style or delayed sleep phase), or offer detailed strategies for the management of substance use or physical health.

Disturbances in sleep and circadian rhythmicity (CR) are frequent in individuals with bipolar disorders (BD). Very few studies explored the associations between psychotropic medications and these disturbances in euthymic BD. Therefore, we aimed at exploring the associations between several classes of medications (lithium, sedative/non-sedative Atypical Antipsychotics (AAP), anticonvulsants, antidepressants, benzodiazepines) and sleep disturbances and CR dimensions in a sample of euthymic individuals with BD. We included euthymic adults with BD type 1 or 2 assessed with 21 days of actimetry. We used a Principal Component Analysis (PCA) of sleep and CR estimates to generate dimensions to be studied in association with the current use of psychotropic medications, with adjustments for potential confounding factors. We included individuals with BD-1 (n = 116) or BD-2 (n = 37). The PCA led to four dimensions of sleep and CR estimates. Benzodiazepines were associated with better sleep quality (p corrected = 0.032). Aripiprazole was associated with less robust CR (p corrected = 0.016), but with earlier peak of activity patterns (p corrected = 0.020). Sedative AAPs were associated with better sleep quality, which was no longer significant after correction. We found no association between lithium or anticonvulsants and CR. The cross-sectional design and the possible non-representativeness of the sample were limitations of our study. In euthymic individuals with BD, benzodiazepines may have a positive effect on sleep quality, while aripiprazole may have mixed effects on CR (less robust but with earlier peak of activity patterns). No association with lithium or anticonvulsants observed. Further studies are warranted to replicate and extend these results. • Few studies explored associations between psychotropic drugs and actigraphy in BD. • Benzodiazepines are associated with higher sleep quality. • Non-sedative atypical antipsychotics are associated with less robust CR but earlier peak of activity patterns. • No association between lithium or anticonvulsants and circadian rhythms was observed. • Cross-sectional design and heterogeneity of treatment are limitations in this study. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorders are serious mental illnesses, yet evidence suggests that the diagnosis and treatment of bipolar disorder can be delayed by around 6 years. Aim: To identify signals of undiagnosed bipolar disorder using routinely collected electronic health records. Design and setting: A nested case–control study conducted using the UK Clinical Practice Research Datalink (CPRD) GOLD dataset, an anonymised electronic primary care patient database linked with hospital records. 'Cases' were adult patients with incident bipolar disorder diagnoses between 1 January 2010 and 31 July 2017. Method: The patients with bipolar disorder (the bipolar disorder group) were matched by age, sex, and registered general practice to 20 'controls' without recorded bipolar disorder (the control group). Annual episode incidence rates were estimated and odds ratios from conditional logistic regression models were reported for recorded health events before the index (diagnosis) date. Results: There were 2366 patients with incident bipolar disorder diagnoses and 47 138 matched control patients (median age 40 years and 60.4% female: n = 1430/2366 with bipolar disorder and n = 28 471/47 138 without). Compared with the control group, the bipolar disorder group had a higher incidence of diagnosed depressive, psychotic, anxiety, and personality disorders and escalating self-harm up to 10 years before a bipolar disorder diagnosis. Sleep disturbance, substance misuse, and mood swings were more frequent among the bipolar disorder group than the control group. The bipolar disorder group had more frequent face-to-face consultations, and were more likely to miss multiple scheduled appointments and to be prescribed ≥3 different psychotropic medication classes in a given year. Conclusion: Psychiatric diagnoses, psychotropic prescriptions, and health service use patterns might be signals of unreported bipolar disorder. Recognising these signals could prompt further investigation for undiagnosed significant psychopathology, leading to timely referral, assessment, and initiation of appropriate treatments. [ABSTRACT FROM AUTHOR]