Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder.

BACKGROUND: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. METHODS: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. RESULTS: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. CONCLUSION: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

COPD Positive Screening with Spirometry Increases Motivation to Quit Tobacco Smoking in an Addiction Treatment Center.

Providing an on-site immediate diagnosis of Chronic Obstructive Pulmonary Disease (COPD) and lung age in tobacco smokers could be a motivational tool for smoking cessation. Our aim was to investigate the effects of an abnormal spirometry results on motivational change and subsequent smoking cessation. We conducted a retrospective analysis of smoking status after 3 months of tobacco counseling. Patients were recruited in an addiction outpatient center. Spirometry results were obtained with a portable device during the first visit. The sample was thus divided in 3 groups: COPD, subthreshold-group (no COPD but abnormal lung age) and normal spirometry. Among the three groups, we compared the immediate motivation change, difference in Q-MAT motivation scale score after minus before spirometry (Kruskal-Wallis test) and the smoking status after 3 months (Fisher test). We included 48 patients (37 males, median age 44 years, median cigarette-per-day 20). Spirometry results divided the sample in COPD (N = 13), subthreshold (N = 11) and normal group (N = 24). Mean Q-MAT score change after spirometry was different between groups (p = 0.019), greater in COPD (4.62 ± 3.38) than normal group (1.46 ± 3.11), and lower in patient with a co-occuring hazardous alcohol use (p = 7.6 × 10-3). Three-months smoking status was different between spirometry results groups (p = 0.0021). COPD (5/13, 38.5%) and subthreshold patients (6/10, 60.0%) had stopped more frequently than patients from the normal-group (2/22, 9.1%). The effect of immediate spirometry results on motivation to quit varies according to the screened pulmonary damages and hazardous alcohol use. It could be a useful tool in addiction treatment centers.

Association between coffee, tobacco, and alcohol daily consumption and sleep/wake cycle: an actigraphy study in euthymic patients with bipolar disorders.

Individuals with bipolar disorder (BD) have higher than average rates of coffee, tobacco and alcohol use. These substances may have deleterious effects on sleep quality and quantity, which may destabilize sleep/wake cycles and negatively impact the clinical course and prognosis of BD. The use of these substances may also be perceived as a self-medication attempt, for example, to induce sleep or to increase vigilance during the day. The objective of the current study was to investigate associations between the self-reported daily use of coffee, tobacco, and alcohol, and objective measures of sleep and activity patterns in adult individuals with BD. A sample of 147 euthymic individuals with BD were assessed for daily coffee, tobacco and alcohol consumption and 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and daytime activity were compared between groups classified as coffee+/coffee-, tobacco+/tobacco- and alcohol+/alcohol-, defined according to their current daily use. Then, we examined potential correlations between sleep/wake cycle parameters and the amount of daily consumption of each substance. Multivariable analyses identified associations between the use of coffee, tobacco, and alcohol and several sleep and activity parameters, such as between coffee, alcohol, and the relative amplitude of activity (respectively, p = .003 and p = .005), between alcohol and M10 onset (onset time of the 10 most active hours during the 24-h cycle) (p = .003), and between coffee and sleep duration (p = .047). This study supports the hypothesis that there is a relationship, whose direction would be bidirectional, between the daily use of these substances and the sleep/wake cycle in euthymic individuals with BD. These preliminary results require replications in other retrospective and prospective samples. They may have a clinical impact on psycho-education strategies to be proposed to individuals with BD.

Bright Light Therapy in the Morning or at Mid-Day in the Treatment of Non-Seasonal Bipolar Depressive Episodes (LuBi): Study Protocol for a Dose Research Phase I / II Trial.

Objective This study protocol aims to determine, using a rigorous approach in patients with bipolar disorder (BD) and non-seasonal major depressive episode (MDE), the characteristics of bright light therapy (BLT) administration (duration, escalation, morning and mid-day exposures) depending on the tolerance (hypomanic symptoms). Methods Patients with BD I or II and treated by a mood stabilizer are eligible. After 1 week of placebo, patients are randomized between either morning or mid-day exposure for 10 weeks of active BLT with glasses using a dose escalation at 7.5, 10, 15, 30 and 45 minutes/day. A further follow-up visit is planned 6 months after inclusion. Patients will be included by cohorts of 3, with at least 3 days of delay between them, and 1 week between cohorts. If none meet a dose limiting toxicity (DLT; i.e hypomanic symptoms), the initiation dose of the next cohort will be increased. If one patient meet a DLT, an additionnal cohort will start at the same dose. If 2 or 3 patients meet a DLT, from the same cohort or from two cohorts at the same dose initiation, the maximum tolerated dose is defined. This dose escalation will also take into account DLTs observed during the intra-subject escalation on previous cohorts, with a "Target Ceiling Dose" defined if 2 DLTs occured at a dose. Discussion Using an innovative and more ergonomic device in the form of glasses, this study aims to better codify the use of BLT in BD to ensure a good initiation and tolerance. Trial registrationaaClinicalTrials.gov Identifier: NCT03396744.

Anxiety disorders are associated with early onset of heroin use and rapid transition to dependence in methadone maintained patients.

Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.

[Other therapeutic strategies]. / Dépression résistante : les autres stratégies thérapeutiques.

Non-selective and irreversible MAOI have become as third or fourth-line strategy for the management of treatment-resistant depression. Non-selective and irreversible MAOI requires careful monitoring of drug interactions and dietary restrictions. Nutritional supplements such as omega-3 have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment. The glutamate antagonist ketamine has been found to produce beneficial effects in the management of treatment-resistant depression while administered alone. Dopamine and/or norepinephrine agonists, such as methylphenidate, modafinil or pramipexole, have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment.

Sleep- and circadian rhythm-associated pathways as therapeutic targets in bipolar disorder.

INTRODUCTION: Disruptions in sleep and circadian rhythms are observed in individuals with bipolar disorders (BD), both during acute mood episodes and remission. Such abnormalities may relate to dysfunction of the molecular circadian clock and could offer a target for new drugs. AREAS COVERED: This review focuses on clinical, actigraphic, biochemical and genetic biomarkers of BDs, as well as animal and cellular models, and highlights that sleep and circadian rhythm disturbances are closely linked to the susceptibility to BDs and vulnerability to mood relapses. As lithium is likely to act as a synchronizer and stabilizer of circadian rhythms, we will review pharmacogenetic studies testing circadian gene polymorphisms and prophylactic response to lithium. Interventions such as sleep deprivation, light therapy and psychological therapies may also target sleep and circadian disruptions in BDs efficiently for treatment and prevention of bipolar depression. EXPERT OPINION: We suggest that future research should clarify the associations between sleep and circadian rhythm disturbances and alterations of the molecular clock in order to identify critical targets within the circadian pathway. The investigation of such targets using human cellular models or animal models combined with 'omics' approaches are crucial steps for new drug development.