Pierre-Alexis Geoffroy

Sleep in patients with remitted bipolar disorders: a meta‐analysis of actigraphy studies

Sleep dysregulation is highly prevalent in bipolar disorders (BDs), with previous actigraphic studies demonstrating sleep abnormalities during depressive, manic, and interepisode periods. We undertook a meta‐analysis of published actigraphy studies to identify whether any abnormalities in the reported sleep profiles of remitted BD cases differ from controls.

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.

Links between sleep and body mass index in bipolar disorders: An exploratory study ☆

STUDY OBJECTIVES Obesity and excess bodyweight are highly prevalent in individuals with bipolar disorders (BD) and are associated with adverse consequences. Multiple factors may explain increased bodyweight in BD including side effects of psychotropic medications, and reduced physical activity. Research in the general population demonstrates that sleep disturbances may also contribute to metabolic burden. We present a cross-sectional study of the associations between body mass index (BMI) and sleep parameters in patients with BD as compared with healthy controls (HC). METHODS Twenty-six French outpatients with remitted BD and 29 HC with a similar BMI completed a 21-day study of sleep parameters using objective (actigraphy) and subjective (PSQI: Pittsburgh Sleep Quality Index) assessments. RESULTS In BD cases, but not in HC, higher BMI was significantly correlated with lower sleep efficiency (P=0.009) and with several other sleep parameters: shorter total sleep time (P=0.01), longer sleep onset latency (P=0.05), higher fragmentation index (P=0.008), higher inter-day variability (P=0.05) and higher PSQI total score (P=0.004). CONCLUSIONS The findings suggest a link between a high BMI and several sleep disturbances in BD, including lower sleep efficiency. Physiological mechanisms in BD cases may include an exaggeration of phenomena observed in non-clinical populations. However, larger scale studies are required to clarify the links between metabolic and sleep-wake cycle disturbances in BD.

The Bidirectional Relation Between Emotional Reactivity and Sleep: From Disruption to Recovery.

Sleep disturbances are highly prevalent and greatly affect consecutive emotional reactivity, while sleep quality itself can be strongly affected by reactions to previous emotional events. In this review, we shed light on this bidirectional relation through examples of pathology: insomnia and bipolar disorder. We show that both experimental sleep deprivation and insomnia are related to increased emotional reactivity and increased amygdala activation upon emotional stimuli presentation, and that particularly Rapid Eye Movement (REM) sleep is important for emotional processing and reorganization of emotion-specific brain activity. Increased emotional reactivity affects REM sleep quality and sleep spindles, while REM sleep is particularly affected in insomnia, possibly related to condition-specific hyperarousal levels. Normal sleep onset deactivation of brain regions important for emotional processing (amygdala, anterior cingulate cortex (ACC)) is further affected in insomnia. In bipolar disorder, sleep disturbances are common in both symptomatic and nonsymptomatic phases. Both amygdala and ACC volume and function are affected in bipolar disorder, with the ACC showing phase-dependent resting state activity differences. Deficient Gamma-aminobutyric acid (GABA) GABA-ergic activity of this region might play a role in sleep disturbances and their influence on emotional reactivity, given the inhibitory role of GABA on brain activity during sleep and its deficiency in both bipolar disorder and insomnia. Promising findings of normalizing brain activity in both insomnia and bipolar disorder upon treatment may inspire a focus on treatment studies investigating the normalization of sleep, emotional reactivity, and their corresponding brain activity patterns. (PsycINFO Database Record

Residual depressive symptoms, sleep disturbance and perceived cognitive impairment as determinants of functioning in patients with bipolar disorder

BACKGROUND Many patients with bipolar disorder (BD) experience residual symptoms during their inter-episodic periods. The study aimed to analyse the relationship between residual depressive symptoms, sleep disturbances and self-reported cognitive impairment as determinants of psychosocial functioning in a large sample of euthymic BD patients. METHODS This was a cross-sectional study of 468 euthymic BD outpatients. We evaluated the residual depressive symptoms with the Bipolar Depression Rating Scale, the sleep disturbances with the Pittsburgh Sleep Quality Index, the perceived cognitive performance using visual analogic scales and functioning with the Functioning Assessment Short Test. Structural equation modelling (SEM) was used to describe the relationships among the residual depressive symptoms, sleep disturbances, perceived cognitive performance and functioning. RESULTS SEM showed good fit with normed chi square=2.46, comparative fit index=0.94, root mean square error of approximation=0.05 and standardized root mean square residuals=0.06. This model revealed that residual depressive symptoms (path coefficient =0.37) and perceived cognitive performance (path coefficient=0.27) were the most important features significantly related to psychosocial functioning. Sleep disturbances were indirectly associated with functioning via residual depressive symptoms and perceived cognitive performance (path coefficient=0.23). CONCLUSIONS This study contributes to a better understanding of the determinants of psychosocial functioning during the inter-episodic periods of BD patients. These findings should facilitate decision-making in therapeutics to improve the functional outcomes of BD during this period.

Transcranial direct-current stimulation (tDCS) for bipolar depression: A systematic review and meta-analysis

Objective: Bipolar disorder (BD) is a severe and recurrent brain disorder that can manifest in manic or depressive episodes. Transcranial Direct Current Stimulation (tDCS) has been proposed as a novel therapeutic modality for patients experiencing bipolar depression, for which standard treatments are often inefficient. While several studies have been conducted in this patient group, there has been no systematic review or meta‐analysis that specifically examines bipolar depression. We aimed to address this gap in the literature and evaluated the efficacy and tolerability of tDCS in patients fulfilling DSM‐IV‐TR criteria for BD I, II, or BD not otherwise specified (NOS). Methods: We systematically searched the literature from April 2002 to November 2016 to identify relevant publications for inclusion in our systematic review and meta‐analysis. Effect sizes for depression rating‐scale scores were expressed as the standardized mean difference (SMD) before and after tDCS. Results: Thirteen of 382 identified studies met eligibility criteria for our systematic review. The meta‐analysis included 46 patients from 7 studies with depression rating‐scale scores pre‐ and post‐tDCS. Parameters of tDCS procedures were heterogeneous. Depression scores decreased significantly with a medium effect size after acute‐phase of treatment (SMD 0.71 [0.25–1.18], z = 3.00, p = 0.003) and at the furthest endpoint (SMD 1.27 [0.57–1.97], z = 3.57, p = 0.0004). Six cases of affective switching under tDCS treatment protocols were observed. Conclusions: Depressive symptoms respond to tDCS in patients with BD. Additional studies, and particularly randomized controlled trials, are needed to clarify the effectiveness of tDCS in bipolar depression, the frequency of tDCS‐emergent hypomania/mania, and which tDCS modalities are most efficient. HIGHLIGHTStDCS significantly improves symptoms of bipolar depression.tDCS can potentially cause a manic switch in patients with bipolar depression.RCT comparing tDCS antidepressant effect vs placebo are required to explore the effectiveness of tDCS in bipolar depression.

Reply: Sleep in Patients with Remitted Bipolar Disorders: Analyses stratified on actigraphy devices, age and gender

remitted bipolar disorder: a naturalistic case-control study using actigraphy. J Affect Disord 2014;158:1–7. 4. Kaplan KA, Talbot LS, Gruber J, Harvey AG. Evaluating sleep in bipolar disorder: comparison between actigraphy, polysomnography, and sleep diary. Bipolar Disord 2012;14:870–879. 5. Boudebesse C, Geoffroy PA, Bellivier F et al. Correlations between objective and subjective sleep and circadian markers in remitted patients with bipolar disorder. Chronobiol Int 2014;31:698–704.

Prevalence and predictors of no lifetime utilization of mental health treatment among people with mental disorders in France: findings from the ‘Mental Health in General Population’ (MHGP) survey

PurposeNo lifetime utilization of mental health treatment (NUMT) is an indicator of the treatment gap among people in need of treatment. Until now, the overall prevalence and predictors of NUMT have never been explored in France.MethodsIn a 39,617-respondent survey, participants were assessed for NUMT, i.e., no lifetime psychotherapy, psychopharmacotherapy, or psychiatric hospitalization. Mental disorders were investigated using the Mini International Neuropsychiatric Interview (MINI 5.0.0). MINI diagnoses were grouped into five categories: mood disorders (MDs); anxiety disorders (ADs); alcohol use disorders (AUDs); substance use disorders (SUDs); and psychotic disorders (PDs). Using multivariable logistic regression models, we explored the factors associated with NUMT among the MINI-positive respondents. The odds ratio and 95% confidence interval were calculated for each factor.ResultsIn total, 12,818 (32.4%) respondents were MINI-positive, 46.5% of them reported NUMT (35.6% for MDs, 39.7% for PDs, 42.8% for ADs, 56.0% for AUDs, and 56.7% for SUDs). NUMT was positively associated with being male [OR 1.75 (1.59–1.91)] and practising religion [OR 1.13 (1.02–1.25)] and negatively associated with ageing [per 10-year increase: OR 0.88 (0.85–0.91)], being single [OR 0.74 (0.66–0.84)], being a French native [OR 0.67 (0.60–0.75)], and experiencing MDs [OR 0.39 (0.36–0.43)], ADs [OR 0.47 (0.43–0.52)], AUDs [OR 0.83 (0.73–0.96)], SUDs [OR 0.77 (0.65–0.91)], or PDs [OR 0.50 (0.43–0.59)].ConclusionsIn France, NUMT rates were the highest for AUDs and SUDs. Additionally, suffering from MDs or ADs increased the lifetime treatment utilization for people having any other mental disorder. This finding emphasizes the need to better screen AUDs and SUDs among people treated for MDs or ADs.

Metabolic syndrome and actigraphy measures of sleep and circadian rhythms in bipolar disorders during remission

This study explored the correlations between sleep and circadian rhythm measures and the metabolic syndrome (MetS) components in remitted patients with bipolar disorder (BD).

1473 – Seasonal pattern in bipolar disorder: prevalence, clinical characteristics and gender influence

Introduction Circadian rhythm pathways are highlighted in a number of etiological models of bipolar disorder (BD). More than 25% of bipolar patients may present seasonal pattern (SP). However, there is very limited scientific data on the prevalence of SP, its clinical manifestations and any gender influence. Methods Caucasian individuals who met DSM-IV criteria for BD I or II were recruited from three university-affiliated psychiatric departments in France (Paris, Bordeaux, Nancy). SP was defined according to DSM-IV criteria. Clinical and socio- demographic variables were obtained from structured interviews with the patients and their relatives. Results Four hundred and fifty-two bipolar patients (n=452) in euthymic state were included in the study, 102 of them (23%) were considered as having SP according to DSM-IV criteria. Multivariate analysis showed a significant association of BD patients with SP for bipolar II subtype (OR=1.99, p=0.013), rapid cycling (OR=2.04, p=0.02), eating disorder (OR=2.93, p=0.003) and the total number of depressive episodes (OR=1.12, p=0.002). 71% of cases were correctly classified by this analysis. However, when stratifying the analyses by gender, SP was associated with BD II subtype (OR=2.89, p=0.02) and total number of depressive episodes (OR=1.21, p=0.002) in males but with rapid cycling (OR=3.02, p=0.003) and eating disorders (OR=2.60, p=0.02) in females. Conclusions The high prevalence of SP in BD, its associated clinical characteristics and the observed differences between genders, suggest that SP represents a potentially important specifier of BD.