Role of Melatonin in the Management of Sleep and Circadian Disorders in the Context of Psychiatric Illness.

PURPOSE OF REVIEW: We present a review of research on the role of melatonin in the management of sleep and circadian disorders, stressing current overall view of the knowledge across psychiatric disorders. RECENT FINDINGS: Dysregulation of sleep and circadian rhythms has been established in several psychiatric and neurocognitive disorders for long. Recent research confirms this finding consistently across disorders. The secretion of melatonin in schizophrenia and neurocognitive disorders is reduced due to a smaller volume and enlarged calcification of the pineal gland. On the other hand, melatonin dysregulation in bipolar disorder may be more dynamic and caused by light-sensitive melatonin suppression and delayed melatonin secretion. In both cases, exogenous melatonin seems indicated to correct the dysfunction. However, a very limited number of well-designed trials with melatonin to correct sleep and circadian rhythms exist in psychiatric disorders, and the evidence for efficacy is robust only in autism, attention deficit hyperactivity disorder (ADHD), and neurocognitive disorders. This topic has mainly not been of interest for recent work and well-designed trials with objective circadian parameters are few. Overall, recent studies in psychiatric disorders reported that melatonin can be effective in improving sleep parameters such as sleep onset latency, sleep efficiency, and sleep quality. Recent meta-analysis suggests that optimal dosage and dosing time might be important to maximize the efficacy of melatonin. The knowledge base is sufficient to propose well-designed, larger trials with circadian parameters as inclusion and outcome criteria. Based on the partly fragmentary information, we propose testing efficacy in disorders with neurocognitive etiopathology with later and higher dosing, and affective and anxiety disorders with lower and earlier dosing of melatonin. Melatonin is promising for the correction of sleep and circadian abnormalities in psychiatric disorders. However, research results on its effect are still few and need to be accumulated. For effective use of melatonin, it is necessary to consider the appropriate dosage and administration time, depending on the individual abnormality of sleep and circadian rhythms.

Atorvastatin lowers serum calcium levels in lithium-users: results from a randomized controlled trial.

BACKGROUND: Although lithium is considered the gold-standard treatment for bipolar disorder (BD), it is associated with a variety of major endocrine and metabolic side effects, including parathyroid hormone (PTH) dependent hypercalcemia. Aside from surgery and medication discontinuation, there are limited treatments for hypercalcemia. This paper will assess data from a randomized controlled trial (RCT). METHODS: This is a secondary analysis of an RCT that explored the effects of atorvastatin (n = 27) versus placebo (n = 33) on lithium-induced nephrogenic diabetes insipidus (NDI) in patients with BD and major depressive disorder (MDD) using lithium (n = 60), over a 12-week period. This secondary analysis will explore serum calcium levels and thyroid stimulating hormone (TSH) measured at baseline, week 4, and week 12. RESULTS: At 12-weeks follow-up while adjusting results for baseline, linear regression analyses found that corrected serum calcium levels were significantly lower in the treatment group (mean (M) = 2.30 mmol/L, standard deviation (SD) = 0.07) compared to the placebo group (M = 2.33 mmol/L, SD = 0.07) (ß = - 0.03 (95% C.I.; - 0.0662, - 0.0035), p = 0.03) for lithium users. There were no significant changes in TSH. CONCLUSION: In lithium users with relatively normal calcium levels, receiving atorvastatin was associated with a decrease in serum calcium levels. Although exciting, this is a preliminary finding that needs further investigation with hypercalcemic patients. Future RCTs could examine whether atorvastatin can treat PTH dependent hypercalcemia due to lithium and other causes.

Cultural adaptation of an appropriate tool for mental health among Kanien'kehá:ka: a participatory action project based on the Growth and Empowerment Measure.

We present a cultural adaptation of the Growth and Empowerment Measure (GEM) from the Kanien'kehá:ka people of Quebec (Canada). Our aim was to develop a culturally competent and safe tool to assess and promote well-being among this population. We followed a qualitative, collaborative, and participatory method that sought to benefit Indigenous participants and communities, while honouring their culture and philosophies. Twelve adults from health and community services of Kahnawà:ke participated in total five focus group meetings. We carried out a thematic analysis of the data collected through an advisory group that led a revision of the cultural and conceptual relevance of the tool and its content. The group integrated socio-culturally relevant elements and restructured the tool so that it reflected local well-being factors and showed its versatility of being an assessment tool and therapeutic support. A narrative and empowerement-driven approach, culturally based intervention, cultural safety and flexibility when using the instrument were considered successful strategies to improve wellness. This project provides valuable information about the perspectives of local Indigenous communities regarding mental health and factors of empowerment. Mutual understanding and integration of psychological and traditional knowledge can create a beneficial program to improve emotional, mental, spiritual, and physical well-being for the local population. It remains to be tested whether the Kanien'kehá:ka Growth and Empowerment Measure (K-GEM) is clinically useful in psychological and psychiatric intervention, and social and community services.

A double-blind, randomized, placebo-controlled pilot trial of atorvastatin for nephrogenic diabetes insipidus in lithium users.

OBJECTIVE: Lithium remains an important treatment for mood disorders but is associated with kidney disease. Nephrogenic diabetes insipidus (NDI) is associated with up to 3-fold risk of incident chronic kidney disease among lithium users. There are limited randomized controlled trials (RCT) for treatments of lithium-induced NDI, and existing therapies can be poorly tolerated. Therefore, novel treatments are needed for lithium-induced NDI. METHOD: We conducted a 12-week double-blind pilot RCT to assess the feasibility and efficacy of 20 mg/d atorvastatin vs placebo in the treatment of NDI in chronic lithium users. Patients, recruited between September 2017 and October 2018, were aged 18 to 85, currently on a stable dose of lithium, and determined to have NDI. RESULTS: Urinary osmolality (UOsm) at 12 weeks adjusted for baseline was not statistically different between groups (+39.6 mOsm/kg [95% CI, -35.3, 114.5] in atorvastatin compared to placebo groups). Secondary outcomes of fluid intake and aquaporin-2 excretions at 12 weeks adjusted for baseline were -0.13 L [95% CI, -0.54, 0.28] and 98.68 [95% CI, -190.34, 387.70], respectively. A moderate effect size was observed for improvements in baseline UOsm by ≥100 mOsm/kg at 12 weeks in patients who received atorvastatin compared to placebo (38.45% (10/26) vs 22.58% (7/31); Cohen's d = 0.66). CONCLUSION: Among lithium users with NDI, atorvastatin 20 mg/d did not significantly improve urinary osmolality compared to placebo over a 12-week period. Larger confirmatory trials with longer follow-up periods may help to further assess the effects of statins on NDI, especially within patients with more severe NDI.

Relevance of Objective Measures in Psychiatric Disorders-Rest-Activity Rhythm and Psychophysiological Measures.

PURPOSE OF REVIEW: We present a review of recent methods of objective measurement in psychiatry and psychology with a focus on home monitoring and its utility in guiding treatment. RECENT FINDINGS: For individualized diagnostics and treatment of insomnia, actigraphy can generate clinically useful graphical presentations of sleep timing and patterns. Psychophysiological measures may complement psychometrics by tracking parallel changes in physiological responses and emotional functioning, especially during therapy for trauma symptoms and emotion regulation. It seems that rather than defining universal cut-offs, an individualised range of variability could characterize treatment response. Wearable actigraphy and psychophysiological sensors are promising devices to provide biofeedback and guide treatment. Use of feasible and reliable technology during experimental and clinical procedures may necessitate defining healthy and abnormal responses in different populations and pathological states. We present a "call for action" towards further collaborative work to enable large scale use of objective measures.

Irregular eating patterns associate with hypomanic symptoms in bipolar disorders.

Objective: We present novel dimensional methods to describe the timing of eating in psychopathology. We focused on the relationship between current mood in bipolar disorder (BD) and the stability of the temporal pattern of daily eating events. Methods: Consenting BD patients (n = 69) from an outpatient, tertiary care clinic completed hourly charts of mood and eating for two weeks. Mood was also evaluated with Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). Results: Illustrative displays, or eatograms, enabling visualization of all recorded eating events were used to guide assessment of the temporal structure of eating across the two week assessment period. We computed indices to quantify irregularities in timing of eating, namely IFRQ, ITIM and IINT for the variability of frequency, timing, and interval of eating events, respectively. In this cohort, irregular temporal pattern of eating correlated with hypomanic symptoms (YMRS with IFRQ, Spearman rank order rh = 0.28, p = .019, with ITIM, rh = 0.44, p < .001, and with IINT rh = 0.38, p = .001), but not depressive symptoms or anthropometric measures. Conclusions: Our data suggest a link between the instability of the temporal order of daily eating and mood. The dimensional measures for eating pattern introduced here enable future investigations of correlations with psychopathology.

Obesity and metabolic comorbidity in bipolar disorder: do patients on lithium comprise a subgroup? A naturalistic study.

BACKGROUND: Bipolar disorders (BD) are associated with increased prevalence of obesity and metabolic syndrome (MetS). Nevertheless, there is a wide range in prevalence estimates, with little known about the contributions of pharmacotherapy. It has been suggested that lithium might have a more favorable metabolic profile. We hypothesized that lithium use is associated with less increased body mass index (BMI), MetS, and type II diabetes, when compared with non-lithium users (those on anticonvulsants, second-generation antipsychotics). METHODS: Cross-sectional study of 129 patients aged 18-85 with bipolar disorder, followed at tertiary care clinics in Montreal. Patients using lithium were compared with those not on lithium, for body mass index and metabolic syndrome. RESULTS: The prevalence of obesity and metabolic syndrome in the sample of lithium-using patients with BD was 42.4 and 35.7% respectively, with an average BMI of 29.10 (+/- 6.70). Lithium and non-lithium groups did not differ in BMI or prevalence of MetS. However, compared to the non-lithium group, lithium users had lower hemoglobin A1C (5.24 +/- 0.53 versus 6.01 +/- 1.83, U = 753.5, p = 0.006) and lower triglycerides (1.46 +/- 0.88 versus 2.01 +/- 1.25, U = 947, p = 0.020). CONCLUSIONS: There is a high prevalence of obesity and metabolic syndrome among patients with bipolar disorder. However, this did not appear to be associated with lithium use, when compared to those not on lithium. The lithium subgroup was also associated with lower prevalence of type II diabetes. Future prospective and intervention studies with larger sample sizes are necessary to further explore the association between lithium and insulin resistance, as well as its underlying mechanisms.

Depression or resilience? A participatory study to identify an appropriate assessment tool with Kanien'kéha (Mohawk) and Inuit in Quebec.

PURPOSE: We present a study on selection of a psychometric scale to be clinically used among Indigenous people with depression. Our aim was to select a psychometric tool for cultural adaptation with Mohawk and Inuit in Quebec. METHODS: We selected three depression scales and three protective factor scales based on: strong validity for psychometric properties, evidence for good psychometric qualities across translations, avoidance of cognitively complex sentences, brevity, and clarity. We submitted the scales for consultation, and followed qualitative participatory methods with Mohawks of Kahnawake and Inuit from Nunavik living in an urban environment. We collected data through ten focus groups with advisory committees, and carried out a thematic analysis of the information. RESULTS: The advisory groups considered the measurement scales to be unsafe. The major components that hindered their acceptance were: numeric rating, self-evaluation (versus supportive interaction), and a focus on symptoms rather than supportive factors. The participants preferred the Growth and Empowerment Measure due to its empowering approach. They voiced that it is necessary to develop a culturally sensitive and safe tool which facilitates interactions between the person and the practitioner. CONCLUSION: This project provides valuable information about the perspectives of local Indigenous peoples regarding mental health and factors of empowerment and resilience. The ideal tool should be flexible in terms of the content and its use as compared to the conventional psychometric strategies. A tool developed with the Indigenous perspective on wellbeing could be used in psychological and psychiatric intervention as well as in social and community services.

Development and implementation of guidelines for the management of depression: a systematic review.

OBJECTIVE: To evaluate the development and implementation of clinical practice guidelines for the management of depression globally. METHODS: We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries. FINDINGS: We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence. CONCLUSION: Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes.

Inactograms and objective sleep measures as means to capture subjective sleep problems in patients with a bipolar disorder.

BACKGROUND: Sleep problems are common in bipolar disorders (BDs). To objectively characterize these problems in BDs, further methodological development is needed to capture subjective insomnia. AIM: To test psychometric properties of the Athens Insomnia Scale (AIS), and associations with actigraphy-derived measures, applying modifications in actigraphy data processing to capture features of perturbed sleep in patients with a BD. METHODS: Seventy-four patients completed the AIS and the Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR-16). Locomotor activity was continuously recorded by wrist actigraphy for ≥10 consecutive days. We computed the sleep onset/offset, the center of daily inactivity (CenDI), as a proxy for chronotype, and the degree of consolidation of daily inactivity (ConDI), as a proxy for sleep-wake rhythm strength. RESULTS: AIS showed good psychometric properties (Cronbach's alpha = 0.84; test-retest correlation = 0.84, P<.001). Subjective sleep problems correlated moderately with a later sleep phase (CenDI with AIS rho = 0.34, P = .003), lower consolidation (ConDI with AIS rho = -0.22, P = .05; with QIDS-SR-16 rho = -0.27, P = .019), later timing of sleep offset (with AIS rho = 0.49, P = ≤.001, with QIDS-SR-16 rho = 0.36, P = .002), and longer total sleep (with AIS rho = 0.29, P = .012, with QIDS-SR-16 rho = 0.41, P = ≤.001). While AIS was psychometrically more solid, correlations with objective sleep were more consistent across time for QIDS-SR-16. CONCLUSIONS: AIS and QIDS-SR-16 are suitable for clinical screening of sleep problems among patients with a BD. Subjective insomnia associated with objective measures. For clinical and research purposes, actigraphy and data visualization on inactograms are useful for accurate longitudinal characterization of sleep patterns.

Late and Instable Sleep Phasing is Associated With Irregular Eating Patterns in Eating Disorders.

BACKGROUND: Sleep problems are common in eating disorders (EDs). PURPOSE: We evaluated whether sleep-phasing regularity associates with the regularity of daily eating events. METHODS: ED patients (n = 29) completed hourly charts of mood and eating occasions for 2 weeks. Locomotor activity was recorded continuously by wrist actigraphy for a minimum of 10 days, and sleep was calculated based on periods of inactivity. We computed the center of daily inactivity (CenDI) as a measure of sleep phasing and consolidation of the daily inactivity (ConDI) as a measure of daily sleep rhythm strength. We assessed interday irregularities in the temporal structure of food intake using the standard deviation (SD) of frequency (IFRQ), timing (ITIM), and interval (IINT) of food intake. A self-evaluation of other characteristics included mood, anxiety, and early trauma. RESULTS: A later phasing of sleep associated with a lower frequency of eating (eating frequency with the CenDI rho = -0.49, p = .007). The phasing and rhythmic strength of sleep correlated with the degree of eating irregularity (CenDI with ITIM rho = 0.48, p = .008 and with IINT rho = 0.56, p = .002; SD of CenDI with ITIM rho = 0.47, p = .010, and SD of ConDI with IINT rho = 0.37, p = .048). Childhood Trauma Questionnaire showed associations with variation of sleep onset (rho = -0.51, p = .005) and with IFRQ (rho = 0.43, p = .023). CONCLUSIONS: Late and variable phasing of sleep associated robustly with irregular pattern of eating. Larger data sets are warranted to enable the analysis of diagnostic subgroups, current medication, and current symptomatology and to confirm the likely bidirectional association between eating pattern stability and the timing of sleep.

Suicidal Ideation and Insomnia in Bipolar Disorders: Idéation suicidaire et insomnie dans les troubles bipolaires.

OBJECTIVE: Bipolar disorder (BD) confers elevated suicide risk and associates with misaligned circadian rhythm. Real-time monitoring of objectively measured sleep is a novel approach to detect and prevent suicidal behavior. We aimed at understanding associations between subjective insomnia and actigraphy data with severity of suicidal ideation in BDs. METHODS: This prospective cohort study comprised 76 outpatients with a BD aged 18 to 65 inclusively. Main measures included 10 consecutive days of wrist actigraphy; the Athens Insomnia Scale (AIS); the Montgomery-Åsberg Depression Rating Scale (MADRS); the Quick Inventory of Depressive Symptoms-16, self-rating (QIDS-SR-16); and the Columbia Suicide Severity Rating Scale. Diagnoses, medications, and suicide attempts were obtained from chart review. RESULTS: Suicidal ideation correlated moderately with subjective insomnia (AIS with QIDS-SR-16 item 12 ρ =0.26, P = 0.03; MADRS item 10 ρ = 0.33, P = 0.003). Graphical sleep patterns showed that suicidal patients were enriched among the most fragmented sleep patterns, and this was confirmed by correlations of suicidal ideation with actigraphy data at 2 visits. Patients with lifetime suicide attempts (n = 8) had more varied objective sleep (a higher standard deviation of center of daily inactivity [0.64 vs. 0.26, P = 0.01], consolidation of daily inactivity [0.18 vs. 0.10, P = <0.001], sleep offset [3.02 hours vs. 1.90 hours, P = <0.001], and total sleep [105 vs. 69 minutes, P = 0.02], and a lower consolidation of daily inactivity [0.65 vs. 0.79, P = 0.03]). CONCLUSIONS: Subjective insomnia, a nonstigmatized symptom, can complement suicidality screens. Longer follow-ups and larger samples are warranted to understand whether real-time sleep monitoring predicts suicidal ideation in patient subgroups or individually.

Healthcare use of young finnish adults with mental disorders - profiles and profile membership determinants.

BACKGROUND: Comprehensive, timely, and integrated primary care services have been proposed as a response to the increased demand for mental health and substance use services especially among young people. However, little is known about the care utilization patterns of young people with mental and substance use disorders. Our aim was to characterize profiles of care use in young Finnish adults with mental or substance use disorders, and the potential factors associated with the service use profiles. METHODS: Primary and specialized care visits of young adults (16-29 years) diagnosed with a psychiatric or a substance use disorder (n = 7714) were retrieved from the national health care register from years 2020 and 2021. K-Means clustering was used to detect different profiles based on the utilization of care services. Multinomial logistic regression was used to analyze the factors associated with different profiles of care use. RESULTS: Five different profiles were identified: low care use (75%), and use of principally primary health care (11%), student health services (9%), psychiatric services (5%), or substance use services (1%). Female gender was associated with membership in the primary health care focused profiles (OR 2.58 and OR 1.99), and patients in the primary health care and student health services profiles were associated with a better continuity of care (OR 1.04 and OR 1.05). Substance use disorders were associated with psychiatric service use (OR: 2.51) and substance use services (OR: 58.91). Living in smaller municipalities was associated with lower service use when comparing to the largest city. CONCLUSIONS: Young adults diagnosed with a psychiatric or a substance use disorder had remarkably different and heterogeneous care patterns. Most of the participants had low care utilization, indicating potential gaps in service use and care needs. Measures should be taken to ensure equal access to and availability of mental health services. The profiles that utilized the most services highlights the importance of integrated services and patient-oriented improvement of treatment.

Safe and valid? A systematic review of the psychometric properties of culturally adapted depression scales for use among Indigenous populations.

Background: Implementing culturally sensitive psychometric measures of depression may be an effective strategy to improve acceptance, response rate, and reliability of psychological assessment among Indigenous populations. However, the psychometric properties of depression scales after cultural adaptation remain unclear. Methods: We screened the Ovid Medline, PubMed, Embase, Global Health, PsycInfo, and CINAHL databases through three levels of search terms: Depression, Psychometrics, and Indigenous, following the PRISMA guidelines. We assessed metrics for reliability (including Cronbach's alpha), validity (including fit indices), and clinical utility (including predictive value). Results: Across 31 studies included the review, 13 different depression scales were adapted through language or content modification. Sample populations included Indigenous from the Americas, Asia, Africa, and Oceania. Most cultural adaptations had strong psychometric properties; however, few and inconsistent properties were reported. Where available, alphas, inter-rater and test-retest reliability, construct validity, and incremental validity often indicated increased cultural sensitivity of adapted scales. There were mixed results for clinical utility, criterion validity, cross-cultural validity, sensitivity, specificity, area under the receiver operating characteristic curve, predictive value, and likelihood ratio. Conclusions: Modifications to increase cultural relevance have the potential to improve fit and acceptance of a scale by the Indigenous population, however, these changes may decrease specificity and negative predictive value. There is an urgent need for suitable tools that are useful and reliable for identifying Indigenous individuals for clinical treatment of depression. This awaits future work for optimal specificity and validated cut-off points that take into account the high prevalence of depression in these populations.

The methods of improving cultural sensitivity of depression scales for use among global indigenous populations: a systematic scoping review.

Cultural adaptation of psychometric measures has become a process aimed at increasing acceptance, reliability, and validity among specific Indigenous populations. We present a systematic scoping review to: (1) identify the depression scales that have been culturally adapted for use among Indigenous populations worldwide, (2) globally report on the methods used in the cultural adaptation of those scales, and (3) describe the main features of those cultural adaptation methods. We included articles published from inception to April 2021, including 3 levels of search terms: Psychometrics, Indigenous, and Depression. The search was carried out in the Ovid Medline, PubMed, Embase, Global Health, PsycINFO, and CINAHL databases, following PRISMA guidelines. We identified 34 reports on processes of cultural adaptation that met the criteria. The scales were adapted for use among Indigenous populations from Africa, Australia, Asia, North America, and Latin America. The most common scales that underwent adaptation were the Patient Health Questionnaire (PHQ-9), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Edinburgh Postnatal Depression Scale (EPDS). Methods of adaptation involved a revision of the measures' cultural appropriateness, standard/transcultural translation, revision of the administration process, and inclusion of visual supports. Culturally safe administration of scales was reported in some studies. To come to a consensus on most appropriate methods of improving cultural safety of psychometric measurement, most studies utilized qualitative methods or mixed methods to understand the specific community's needs. Revision of linguistic equivalence and cultural relevance of content, culturally safe administration procedures, qualitative methods, and participatory research were key features of developing safe culturally adapted measures for depressive symptoms among Indigenous populations. While for comparability, uniform scales would be ideal as mental health evaluations, an understanding of the cultural impact of measurements and local depression expressions would benefit the process of developing culturally sensitive psychometric scales. PROSPERO registration ID: CRD42023391439.

A Virtual Reality-Assisted Cognitive Behavioral Therapy for and With Inuit in Québec: Protocol for a Proof-of-Concept Randomized Controlled Trial.

BACKGROUND: Emotion regulation is an ability related to psychological well-being; when dysregulated, individuals may have psychiatric symptoms and maladapted physiological responses. Virtual reality-assisted cognitive behavioral therapy (VR-CBT) is an effective psychotherapy to target and strengthen emotion regulation; however, it currently lacks cultural sensitivity and can be improved by adapting it to the cultural context of service users. During previous participatory research, we co-designed a culturally adapted cognitive behavioral therapy (CBT) manual and 2 virtual reality (VR) environments to function as a complement to therapy (VR-CBT) for Inuit who would like to access psychotherapy. Emotion regulation skill building will occur in virtual environments that have interactive components such as heart rate biofeedback. OBJECTIVE: We describe a protocol for a proof-of-concept 2-arm randomized controlled trial (RCT) with Inuit (n=40) in Québec. The primary aims of this research are to investigate the feasibility, benefits, and challenges of the culturally adapted VR-CBT intervention versus an established VR self-management that is available commercially. We will also investigate self-rated mental well-being and objective psychophysiological measures. Finally, we will use proof-of-concept data to identify suitable primary outcome measures, conduct power calculations in a larger trial for efficacy, and collect information about preferences for on-site or at-home treatment. METHODS: Trial participants will be randomly assigned to an active condition or active control condition in a 1:1 ratio. Inuit aged 14 to 60 years will receive a culturally adapted and therapist-guided VR-CBT with biofeedback or a VR relaxation program with nonpersonalized guided components over a 10-week period. We will collect pre- and posttreatment measures of emotion regulation and biweekly assessments over the treatment and at 3-month follow-up. The primary outcome will be measured by the Difficulties in Emotion Regulation Scale (DERS-16) and a novel psychophysiological reactivity paradigm. Secondary measures include psychological symptoms and well-being via rating scales (eg, anxiety or depressive symptoms). RESULTS: As this is the prospective registration of an RCT protocol, we do not yet report any results from the trial. Funding was confirmed in January 2020, and recruitment is expected to start in March 2023 and is set to finish in August 2025. The expected results are to be published in spring 2026. CONCLUSIONS: The proposed study responds to the community's desire for accessible and appropriate resources for psychological well-being, as it was developed in active collaboration with the Inuit community in Québec. We will test feasibility and acceptance by comparing a culturally adapted, on-site psychotherapy with a commercial self-management program while incorporating novel technology and measurement in the area of Indigenous health. We also aim to fulfill the needs for RCT evidence of culturally adapted psychotherapies that are lacking in Canada. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 21831510; https://www.isrctn.com/ISRCTN21831510. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/40236.

Melatonergic agents influence the sleep-wake and circadian rhythms in healthy and psychiatric participants: a systematic review and meta-analysis of randomized controlled trials.

Exogenous melatonergic agents are widely used to treat insomnia and sleep disturbance. Several studies have shown that they might also modulate circadian rhythms. The purpose of this systematic review and meta-analysis was to summarize current knowledge about the effects of melatonin supplements and melatonin agonists on the sleep-wake cycle as well as on the circadian rhythm of melatonin in healthy participants and in patients with psychiatric disorders. The following electronic databases were searched: EMBASE, PubMed, Web of Science, CINAHL, and Cochrane Library. Of the 12,719 articles, we finally selected 30 studies including 1294 healthy participants and 8 studies including 687 patients with psychiatric disorders. Cochrane risk of bias tool was used to assess the risk of bias. Using meta-ANOVA, studies on healthy participants showed advancing effects of melatonergic supplements and agonists on sleep-wake cycle according to dosing time and dosage, despite the fact that the original individual melatonin rhythm was within a normal range (fixed effect model standardized mean difference [95% Confidence Interval] = -0.639[-0.968 to -0.310]). In a limited number of randomized controlled trials with psychiatric patients, the findings seemed similar to those with healthy participants, despite the psychiatric disorders and treatment related factors affecting circadian rhythms. Given the unmet clinical need for evidence-based treatments to correct circadian rhythms in psychiatric disorders, efficacy of melatonergic agents seen in healthy participants, and similarity of findings among psychiatric patients, large scale, well-designed randomized controlled trials are needed to test efficacy on circadian parameters in psychiatric disorders.

Long-term work disability due to type I and II bipolar disorder: findings of a six-year prospective study.

BACKGROUND: Bipolar disorder (BD) is one of the leading causes of disability worldwide. However, the prevalence and predictors of long-term work disability among patients with type I and II BD have scarcely been studied. We investigated the clinical predictors of long-term work disability among patients with BD. METHODS: The Jorvi Bipolar Study (JoBS) is a naturalistic prospective cohort study (n = 191) of adult psychiatric in- and out-patients with DSM-IV type I and II BD in three Finnish cities. Within JoBS we examined the prevalence and predictors of disability pension being granted during a six-year follow-up of the 152 patients in the labor force at baseline and collected information on granted pensions from national registers. We determined the predictors of disability pension using logistic regression models. RESULTS: Over the 6 years, 44% of the patients belonging to the labor force at baseline were granted a disability pension. Older age; type I BD; comorbidity with generalized anxiety disorder, post-traumatic stress disorder or avoidant personality disorder; and duration of time with depressive or mixed symptoms predicted disability pensions. Including disability pensions granted before baseline increased their total prevalence to 55.5%. The observed predictors were similar. CONCLUSION: This regionally representative long-term prospective study found that about half of patients with type I or II bipolar disorder suffer from persistent work disability that leads to disability pension. In addition to the severity of the clinical course and type I bipolar disorder, the longitudinal accumulation of time depressed, psychiatric comorbidity, and older age predicted pensioning.

Evaluating the perceived utility of an artificial intelligence-powered clinical decision support system for depression treatment using a simulation center.

Aifred is a clinical decision support system (CDSS) that uses artificial intelligence to assist physicians in selecting treatments for major depressive disorder (MDD) by providing probabilities of remission for different treatment options based on patient characteristics. We evaluated the utility of the CDSS as perceived by physicians participating in simulated clinical interactions. Twenty physicians who were either staff or residents in psychiatry or family medicine completed a study in which they had three 10-minute clinical interactions with standardized patients portraying mild, moderate, and severe episodes of MDD. During these scenarios, physicians were given access to the CDSS, which they could use in their treatment decisions. The perceived utility of the CDSS was assessed through self-report questionnaires, scenario observations, and interviews. 60% of physicians perceived the CDSS to be a useful tool in their treatment-selection process, with family physicians perceiving the greatest utility. Moreover, 50% of physicians would use the tool for all patients with depression, with an additional 35% noting that they would reserve the tool for more severe or treatment-resistant patients. Furthermore, clinicians found the tool to be useful in discussing treatment options with patients. The efficacy of this CDSS and its potential to improve treatment outcomes must be further evaluated in clinical trials.

Effects of antipsychotics on circadian rhythms in humans: a systematic review and meta-analysis.

Antipsychotics are widely used to treat psychiatric illness and insomnia. However, the etiology of insomnia is multifactorial, including disrupted circadian rhythms. Several studies show that antipsychotics might modulate even healthy circadian rhythms. The purpose of this systematic review is to integrate current knowledge about the effects of antipsychotics on the circadian rhythms in humans, and to conduct a meta- analysis with the available data. Nine electronic databases were searched. We followed the PRISMA guidelines and included randomized controlled trials (RCTs), non-RCTs, case-control studies, case series, and case reports. Of 7,217 articles, 70 were included. The available data was mainly from healthy individuals, or patients having schizophrenia, but the findings showed a transdiagnostic impact on circadian parameters. This was consistently seen as decreased amplitude of cortisol, melatonin, and body temperature. Particularly, a meta-analysis of 16 RCTs measuring cortisol rhythm showed that antipsychotics, especially atypical antipsychotics, decreased the cortisol area under the curve and morning cortisol level, compared to placebo. The data with melatonin or actigraphy was limited. Overall, this evidence about the circadian effect of antipsychotics showed a need for longitudinal, real-time monitoring of specific circadian markers to differentiate a change in amplitude from a shift in phasing, and for knowledge about optimal timing of administration of antipsychotics, according to individual baseline circadian parameters. Standardizing selection criteria and outcome methods could facilitate good quality intervention studies and evidence-based treatment guidelines. This is relevant considering the accumulating evidence of the high prevalence and unfavorable impact of disrupted circadian rhythms in psychiatric disorders.