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Background: Nutrition is largely affected in bipolar disorder (BD), however, there is a lack of understanding on the relationship between dietary categories, BD, and the prevalence of metabolic syndrome. The objective of this study is to examine dietary trends in BD and it is hypothesized that diets with increased consumption of seafood and high-fiber carbohydrates will be correlated to improved patient outcomes, and a lower frequency of metabolic syndrome., Methods: This retrospective cohort study includes two French cohorts. The primary cohort, FACE-BD, includes 268 stable BD patients. The second cohort, I-GIVE, includes healthy controls, both stable and acute BD and schizophrenia patients. Four dietary categories were assessed: meat, seafood, low-fiber and high-fiber carbohydrates. Dietary data from two food frequency questionnaires were normalized using min-max scaling and assessed using various statistical analyses., Results: In our primary cohort, the increased high-fiber carbohydrate consumption was correlated to lower prevalence of metabolic syndrome and improved mood. Low-fiber carbohydrate consumption is associated with higher BMI, while higher seafood consumption was correlated to improved mood and delayed age of onset. Results were not replicated in our secondary cohort., Limitations: Our populations were small and two different dietary questionnaires were used; thus, results were used to examine similarities in trends., Conclusions: Overall, various dietary trends were associated with metabolic syndrome, BMI, lactate, mood and age of onset. Improving our understanding of nutrition in BD can provide mechanistic insight, clinically relevant nutritional guidelines for precision medicine and ultimately improve the quality of lives for those with BD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities., Competing Interests: Declaration of competing interest Kassandra A. Zachos: none Jaehyoung Choi: none Ophelia Godin: none Timofei Chernega: none Haejin Angela Kwak: none Jae H. Jung: none Bruno Aouizerate: none Valérie Aubin: none Frank Bellivier: none Raoul Belzeaux R: none Philippe Courtet: none Caroline Dubertret: none Bruno Etain: none Emmanuel Haffen: none Antoine Lefrere A: none Pierre-Michel Llorca: none Emilie Olié: none Mircea Polosan: none Ludovic Samalin: none Raymund Schwan: none Paul Roux: none Caroline Barau: none Jean Romain Richard: none Ryad Tamouza: none Ana C. Andreazza: none Marion Leboyer: none, (Copyright © 2024. Published by Elsevier B.V.)

Background: Growing evidence suggests the presence of white matter (WM) alterations in bipolar disorder (BD). In this study we aimed to investigate the state of WM structures, in terms of tissue integrity and morphological complexity, in BD patients compared to healthy controls (HC), in an attempt to better elucidate the microstructural changes associated with BD., Methods: We collected a dataset of 399 Diffusion Tensor Magnetic Resonance Imaging (167 BD and 232 healthy controls) images, acquired at five different sites, which was processed with Tract-Based Spatial Statistics (TBSS) and fractal analysis., Results: The TBSS analysis demonstrated significantly lower FA values in the BD group. Diffusion abnormalities were primarily located in the temporo-parietal network. The Fractal Dimension (FD) analysis did not reveal consistent significant differences in the morphological complexity of WM structures between the groups. When the FD values of patients were considered individually, it is possible to notice some localized significant deviations from the healthy population., Limitations: DTI sequences have not been harmonized before acquisition, samples' sizes are heterogeneous., Conclusions: This study, by applying both TBSS and FD analyses, allows to evaluate diffusion and structural alterations of WM at the same time. The evaluation of WM integrity from these two different perspectives could be useful to better understand the pathophysiological and morphological changes underpinning bipolar disorder., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Reward sensitivity is an essential dimension related to mood fluctuations in bipolar disorder (BD), but there is currently a debate around hypersensitivity or hyposensitivity hypotheses to reward in BD during remission, probably related to a heterogeneous population within the BD spectrum and a lack of reward bias evaluation. Here, we examine reward maximization vs. punishment avoidance learning within the BD spectrum during remission., Methods: Patients with BD-I (n = 45), BD-II (n = 34) and matched (n = 30) healthy controls (HC) were included. They performed an instrumental learning task designed to dissociate reward-based from punishment-based reinforcement learning. Computational modeling was used to identify the mechanisms underlying reinforcement learning performances., Results: Behavioral results showed a significant reward learning deficit across BD subtypes compared to HC, captured at the computational level by a lower sensitivity to rewards compared to punishments in both BD subtypes. Computational modeling also revealed a higher choice randomness in BD-II compared to BD-I that reflected a tendency of BD-I to perform better during punishment avoidance learning than BD-II., Limitations: Our patients were not naive to antipsychotic treatment and were not euthymic (but in syndromic remission) according to the International Society for Bipolar Disorder definition., Conclusions: Our results are consistent with the reward hyposensitivity theory in BD. Computational modeling suggests distinct underlying mechanisms that produce similar observable behaviors, making it a useful tool for distinguishing how symptoms interact in BD versus other disorders. In the long run, a better understanding of these processes could contribute to better prevention and management of BD., Competing Interests: Declaration of competing interest FV has been invited to scientific meetings, consulted and/or served as speaker and received compensation by Lundbeck, Servier, Recordati, Janssen, Otsuka, LivaNova, and Chiesi. He has received research support by Lundbeck and LivaNova. None of these links of interest are related to this work. AP, CD, MG, MP, JB declare that no competing interests exist., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bipolar disorder (BD) is a chronic and severe psychiatric disorder associated with significant medical morbidity and reduced life expectancy. In this study, we assessed accelerated epigenetic aging in individuals with BD using various DNA methylation (DNAm)-based markers. For this purpose, we used five epigenetic clocks (Horvath, Hannum, EN, PhenoAge, and GrimAge) and a DNAm-based telomere length clock (DNAmTL). DNAm profiles were obtained using Infinium MethylationEPIC Arrays from whole-blood samples of 184 individuals with BD. We also estimated blood cell counts based on DNAm levels for adjustment. Significant correlations between chronological age and each epigenetic age estimated using the six different clocks were observed. Following adjustment for blood cell counts, we found that the six epigenetic AgeAccels (age accelerations) were significantly associated with the body mass index. GrimAge AgeAccel was significantly associated with male sex, smoking status and childhood maltreatment. DNAmTL AgeAccel was significantly associated with smoking status. Overall, this study showed that distinct epigenetic clocks are sensitive to different aspects of aging process in BD. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings of potential determinants of an accelerated epigenetic aging in BD., Competing Interests: Declaration of Competing Interest None to be declared in links with this study., (Copyright © 2023. Published by Elsevier B.V.)

Background: Eating disorders (EDs) are liable to alter the disease course of bipolar disorder (BD). We explored the crossed clinical features between EDs and BD, particularly as a function of BD type (BD1 vs. BD2)., Methods: 2929 outpatients attending FondaMental Advanced Centers of Expertise were assessed for BD and lifetime EDs with a semi-structured interview, and their sociodemographic, dimensional and clinical data were collected according to a standardized procedure. For each ED type, bivariate analyses were used to investigate associations between these variables and the type of BD type followed by multinomial regressions with the variables associated with EDs and BDs after Bonferroni correction., Results: Comorbid EDs were diagnosed in 478 (16.4 %) cases, and were more prevalent in patients with BD2 than in those with BD1 (20.6 % vs. 12.4 %, p < 0.001). Regression models showed no difference according to the subtype of bipolar disorder on the characteristics of patients with anorexia nervosa (AN), bulimia nervosa (BN) or binge eating disorder (BED). After multiple adjustments, the factors differentiating BD patients with versus without ED were primarily age, gender, body mass index, more affective lability and comorbidity with anxiety disorders. BD patients with BED also scored higher regarding childhood trauma. BD patients with AN also showed higher risk of past suicide attempts than those with BED., Conclusions: In a large sample of patients with BD, we found a high prevalence of lifetime EDs, especially for the BD2 type. EDs were associated with several severity indicators, but not with BD type-specific characteristics. This should prompt clinicians to carefully screen patients with BD for EDs, regardless of BD and ED types., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests with regard to the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Analyzing cortical folding may provide insight into the biological underpinnings of neurodevelopmental diseases. A neurodevelopmental subtype of bipolar disorders (BD-ND) has been characterized by the combination of early age of onset and psychotic features. We investigate potential cortical morphology differences associated with this subtype. We analyze, for the first time in bipolar disorders, the sulcal pits, the deepest points in each fold of the cerebral cortex., Methods: We extracted the sulcal pits from anatomical MRI among 512 participants gathered from 7 scanning sites. We compared the number of sulcal pits in each hemisphere as well as their regional occurrence and depth between the BD-ND subgroup (N = 184), a subgroup without neurodevelopmental features (BD, N = 77) and a group of healthy controls (HC, N = 251)., Results: In whole brain analysis, BD-ND group have a higher number of sulcal pits in comparison to the BD group. The local analysis revealed, after correction for multiple testing, a higher occurrence of sulcal pits in the left premotor cortex among the BD-ND subgroup compared to the BD and the HC groups., Conclusion: Our findings confirm that BD-ND is associated with a specific brain morphology revealed by the analysis of sulcal pits. These markers may help to better understand neurodevelopment in mood disorder and stratify patients according to a pathophysiological hypothesis., Competing Interests: Declaration of competing interest None of the authors of this manuscript has a conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Suicidal ideation (SI) is a major suicide risk factor; therefore, it is crucial to identify individuals with SI. Discrepancies between the clinicians and patients' estimation of SI may lead to under-evaluating the suicide risk. Yet, studies on discrepancies between self- and clinician-rated SI are lacking, although identifying the patients' sociodemographic and clinical characteristics associated with such discrepancies might help to reduce the under-evaluation risk. Therefore, the aim of this study was to identify features associated with SI rating discrepancies in patients with bipolar disorder (BD) because of the high prevalence of suicide in this population. Among the patients recruited by the French network of FondaMental expert centers for BD, patients with SI (i.e. ≥2 for item 12 of the Quick Inventory of Depressive Symptomatology-Self Report and/or ≥3 for item 10 of the clinician-rated Montgomery and Åsberg Depression Rating Scale) were selected and divided in concordant (i.e. SI in both self- and clinician-rated questionnaires; n = 130; 25.6%), and discordant (i.e. SI in only one questionnaire; n = 377; 74.4%). Depression severity was the feature most associated with SI evaluation discrepancy, especially in patients with SI identified only with the self-rated questionnaire. Clinician may under-evaluate SI presence in patients with low depression level., Competing Interests: Declaration of Competing Interest None of the authors declare conflict of interests related to this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Background: Bipolar disorder (BD) is a severe chronic psychiatric disorder affecting 0.5 to 1% of the population worldwide. To date, most studies have estimated the cost of BD via information sourced from insurance claims with limited information on clinical characteristics and course of BD. The aims of this study are (i) to estimate the direct healthcare cost associated with BD and to identify contributing factors and (ii) to study the evolution of cost during a two-year follow-up period., Method: We analyzed a sample of 1116 individuals with BD included in the Advanced Centers of Expertise in Bipolar Disorder cohort. We estimated the direct healthcare cost per year and per patient, and we identified the clinical features of patients with BD associated with higher direct healthcare costs. In a subsample of patients followed up for two years centers of expertise for BD, we studied the evolution of direct healthcare cost., Results: The average cost of bipolar disorder was € 6910 per year and per patient. Clinical features of BD, sociodemographic characteristics, and associated addiction were associated with higher direct healthcare costs. In the subsample of patients followed-up for two years, direct healthcare cost dropped by more than 50%, strongly suggesting the beneficial effect of specialized care organization., Limitation: We did not estimate indirect healthcare and intangible costs., Conclusion: Our study investigates the cost of BD and its evolution in a deeply phenotyped longitudinal sample. Cost-utility and cost-effectiveness analyses are required to inform resource allocation decisions and to promote innovative healthcare organizations., (Copyright © 2022. Published by Elsevier B.V.)

Background: Bipolar disorder (BD) is a chronic, lifelong condition, associated with increased risk of obesity, cognitive impairment, and suicidal behaviors. Abdominal obesity and a higher risk of violent suicide attempt (SA) seem to be shared correlates with older age, BD, and male sex until middle age when menopause-related female body changes occur. This study aimed at assessing the role of abdominal obesity and cognition in the violent SA burden of individuals with BD., Methods: From the well-defined nationwide cohort FACE-BD (FondaMental Advanced center of Expertise for Bipolar Disorders), we extracted data on 619 euthymic BD patients that were 50 years or older at inclusion. Cross-sectional clinical, cognitive, and metabolic assessments were performed. SA history was based on self-report., Results: Violent SA, in contrast to non-violent and no SA, was associated with higher waist circumference, abdominal obesity and poorer California Verbal Learning Test short-delay free recall (CVLT-SDFR) (ANOVA, p < .001, p = .014, and p = .006). Waist circumference and abdominal obesity were associated with violent SA history independently of sex, BD type and anxiety disorder (Exp(B) 1.02, CI 1.00-1.05, p = .018; Exp(B) 2.16, CI 1.00-4.64, p = .009, accordingly). In an exploratory model, waist circumference and CVLT-SDFR performance mediated the association between male sex and violent SA., Limitations: Cross-sectional design and retrospective reporting., Conclusions: Violent SA history was associated with abdominal obesity and poorer verbal memory in older age BD patients. These factors were interlinked and might mediate the association between male sex and violent SA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: The comorbidity of alcohol use disorder (AUD) and bipolar disorder (BD) has been repeatedly associated with poorer clinical outcomes than BD without AUD. We aimed to extend these findings by focusing on the characteristics associated with the sequence of onset of BD and AUD., Methods: 3,027 outpatients from the Fondamental Advanced Centres of Expertise were ascertained for BD-1, BD-2 and AUD diagnoses, including their respective ages at onset (AAOs, N =2,804). We selected the variables associated with both the presence and sequence of onset of comorbid AUD using bivariate analyses corrected for multiple testing to enter a binary regression model with the sequence of onset of BD and AUD as the dependent variable (AUD first - which also included 88 same-year onsets, vs. BD first)., Results: BD patients with comorbid AUD showed more severe clinical profile than those without. Compared to BD-AUD (N =269), AUD-BD (N =276) was independently associated with a higher AAO of BD (OR =1.1, p <0.001), increased prevalence of comorbid cannabis use disorder (OR =2.8, p <0.001) a higher number of (hypo)manic/mixed BD episodes per year of bipolar illness (OR =3, p <0.01)., Limitations: The transversal design prevents from drawing causal conclusions., Conclusion: Increased severity of BD with AUD compared to BD alone did not differ according to the sequence of onset. A few differences, though, could be used to better monitor the trajectory of patients showing either one of these disorders., (Copyright © 2021. Published by Elsevier B.V.)

Background: Despite thorough and validated clinical guidelines based on bipolar disorders subtypes, large pharmacological treatment heterogeneity remains in these patients. There is limited knowledge about the different treatment combinations used and their influence on patient outcomes. We attempted to determine profiles of patients based on their treatments and to understand the clinical characteristics associated with these treatment profiles., Methods: This multicentre longitudinal study was performed on a French nationwide bipolar cohort database. We performed hierarchical agglomerative clustering to search for clusters of individuals based on their treatments during the first year following inclusion. We then compared patient clinical characteristics according to these clusters., Results: Four groups were identified among the 1795 included patients: group 1 ("heterogeneous" n = 1099), group 2 ("lithium" n = 265), group 3 ("valproate" n = 268), and group 4 ("lamotrigine" n = 163). Proportion of bipolar 1 disorder, in groups 1 to 4 were: 48.2%, 57.0%, 48.9% and 32.5%. Groups 1 and 4 had greater functional impact at baseline and a less favorable clinical and functioning evolution at one-year follow-up, especially on GAF and FAST scales., Limitations: The one-year period used for the analysis of mood stabilizing treatments remains short in the evolution of bipolar disorder., Conclusions: Treatment profiles are associated with functional evolution of patients and were not clearly determined by bipolar subtypes. These profiles seem to group together common patient phenotypes. These findings do not seem to be influenced by the duration of disease prior to inclusion and neither by the number of treatments used during the follow-up period., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder (BD) is a chronic and severe mental illness. It requires a non-discontinued pharmacological treatment to prevent mood recurrences but nonadherence to medication is frequent. To this date, medication adherence in BD has been mostly evaluated in cross-sectional studies and often considered as a stable trait. We aimed to study medication adherence using a prospective person-oriented approach., Methods: 1627 BD patients were followed on a 2 years period and assessed every 6 months. Medication adherence was evaluated at each visit with the Medication Adherence Rating Scale (MARS). A latent class mixed model (LCMM) was used to identify trajectory classes of adherence over time. Regression analyses and linear mixed model were used to search for predictors and covariables of the trajectories., Results: Three distinct and robust trajectories of medication adherence have been identified: one that starts poorly and keeps deteriorating (4.8%), one that starts poorly but improves (9%) and one that starts well and keeps improving (86.2%). A good tolerance to psychotropic medications, low depressive symptoms, the absence of comorbid eating disorders and anticonvulsant medication were associated to a better prognosis of adherence. Along the follow-up, the lower were the depressive symptoms, the better was the medication adherence (p < .001) LIMITATIONS: The use of a single measure of medication adherence although it is a validated instrument and a possible positive selection bias that might limit the generalization of our findings., Conclusions: This study demonstrates that medication adherence in BD patients is a heterogeneous and potentially variable phenomenon., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Impulsivity is commonly assessed using the Barratt Impulsiveness Scale (BIS-11). Some studies challenged the reliability of its three dimensional structure and proposed a bi-dimensional structure., Methods: The psychometric reliability of the BIS-11 scale was studied in a sample of 580 euthymic bipolar patients. An alternative structure of the scale was conceived, using confirmatory factorial analysis (CFA) in the first half (N = 290) and cross-validated in the second half of our sample. Associations between the newly defined shortened scale and predefined clinical variables were computed., Results: The original three dimensional structure did not fit in our sample according to statistical criteria in CFA. A 12 items Impulsivity Scale (IS-12) was designed with strong indices of fitting in the first half of our sample and replicated in the second half of our sample. The IS-12 evidences two dimensions: "behavioral impulsivity" and "cognitive impulsivity". Associations between "behavioral impulsivity" and both presence of past suicide attempts and number of suicide attempts were observed. Substance misuse was strongly associated with both subscores of the new scale., Limitations: The rating of the items assessing the two dimensions of the IS-12 is reversed. The population is restricted to euthymic bipolar patients., Conclusions: The Impulsivity Scale assesses two distinct dimensions named behavioral and cognitive impulsivity. It was reliable and valid in our sample and associated with the existence of suicidal behavior and with substance misuse (alcohol and cannabis). Further studies are needed to demonstrate its predictive validity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Weight gain is a major side effect of antidepressant (AD) drugs. We assessed whether early weight gain is a predictor for long term weight gain in depressed patients treated with antidepressants., Methods: In the six month prospective METADAP cohort, 260 non-overweight patients with a major depressive disorder (MDD), who have recently experienced a Major Depressive Episode (MDE) were assessed for early weight gain (>3%,>5%, and >7%) after one month of treatment, and for long term weight gain (>15% and >20%) after three and six months of treatment. ROC analysis was used to determine the predictive power of early weight gain., Results: 12.4% (21/170) of patients became overweight after three months of treatment and 21.1% (26/123) were overweight after six months. Compared to non-early weight gainers, patients with early weight gain (>3%, >5% and >7%) were 11.3 (OR = 11.3, 95%CI: 4.6-27.6)], 9.9 (OR = 9.9, 95%CI: 3.6-26.9)] and 17.8 (OR = 17.8, 95%CI: 6.4-49.4)] times, respectively, more at risk of late weight gain (>15%). ROC analysis showed that early weight gain (>3%) after one month of treatment, was the best predictor of long term weight gain (≥15%) after three months [Area Under the Curve (AUC )= 87%] and six months of treatment (AUC = 88%) PERSPECTIVES: Given that our baseline sample consisted of strictly non-overweight patients, the 3% threshold for weight gain after one month should be used as an indicator to initiate early weight monitoring in depressed patients treated with antidepressants. High attrition rate remains a limitation in this cohort and other cohorts in psychiatric settings., Disclosures: Bruno Falissard consults for and received lecture fees from for E. Lilly, BMS, Servier, Sanofi-Aventis, GlaxoSmithKline, HRA, Roche, Boeringer Ingelheim, Bayer, Almirall, Allergan, Stallergene, Genzyme, Pierre Fabre, Astra Zeneca, Novartis, Janssen, Astellas, Biotronik, Daiichi-Sankyo, Gilead, MSD, Lundbeck. Florence Gressier received lecture fees from for Servier, Lundbeck and a grant from Servier. Mircea Polosan consults for and received lecture fees from Astra-Zeneca, Bristol Myers Squibb, Lundbeck, Otsuka and Servier. Emmanuel Haffen consults for and received lecture fees from Astra-Zeneca, Bristol Myers Squibb, Pfizer, Lilly, Lundbeck, Otsuka, Sanofi-Aventis, Servier. Philippe Chanson has received unrestricted research and educational grants from Ipsen, Novartis, Novo-Nordisk, and Pfizer for the Department of Endocrinology and Reproductive Diseases, Hôpitaux Universitaires Paris-Sud and for INSERM U 693. He has served as investigator (principal or coordinator) for clinical trials funded by Novartis, Pfizer, Ipsen, Italopharmaco, Antisense, Prolor Biotech. He is member of Advisory Boards from Ipsen, Novartis, Viropharma. He gave lectures for Ipsen, Novartis, Pfizer, NovoNordisk. All the fees and honoraria were paid to his Institution. Bruno Falissard consults for and received lecture fees from NovoNordisk, MSD and Sanofi-Aventis. Laurent Bequemont has close family member working at Sanofi-Aventis, consults for Sanofi-Aventis, Pfizer, Servier and received lecture fees from Genzyme, GlaxoSmithKline, Bristol-Myers Squibb and Merck Sharp and Dohme. Khalil El Asmar, Séverine Trabado, Albane Vievard, Céline Verstuyft, Romain Colle and Emmanuelle Corruble have nothing to declare., (Copyright © 2018. Published by Elsevier B.V.)

Background: 80-90% of patients with Major Depressive Episode (MDE) experience insomnia and up-to 50% severe insomnia. Glycogen Synthase Kinase-3β (GSK3B) is involved both in mood regulation and circadian rhythm. Since GSK3B polymorphisms could affect protein levels or functionality, we investigated the association of GSK3B polymorphisms with insomnia in a sample of depressed patients treated with antidepressants., Methods: In this 6-month prospective real-world treatment study in psychiatric settings (METADAP), 492 Caucasian patients requiring a new antidepressant treatment were included and genotyped for five GSK3B Single Nucleotide Polymorphisms (SNPs) (rs6808874, rs6782799, rs2319398, rs13321783, rs334558). Insomnia and MDE severity were rated using the Hamilton Depression Rating Scale (HDRS). Bi- and multivariate analyses were performed to assess the association between GSK3B SNPs and insomnia (main objective). We also assessed their association with MDE severity and HDRS response/remission after antidepressant treatment., Results: At baseline severe insomnia was associated with the GSK3B rs334558 minor allele (C+) [OR=1.81, CI95%(1.17-2.80), p=0.008]. GSK3B rs334558 C+ had greater insomnia improvement after 6 months of antidepressant treatment (p=0.007, β=0.17, t=2.736). No association was found between GSK3B SNPs and MDE baseline severity or 6-month response/remission., Conclusion: GSK3B rs334558 was associated with insomnia but not with MDE severity in depressed patients. Targeting GSK3B in patients with MDE and a severe insomnia could be a way to improve their symptoms with greater efficiency. And it should be further studied whether the GSK3B-insomnia association may fit into the larger picture of mood disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Hypertriglyceridemia (HTG) is a cardiovascular risk factor. In the general population, elevated fasting triglyceridemia (TG) is associated with insomnia. Since insomnia is a core symptom of Major Depressive Episodes (MDE), we studied the association of severe insomnia with HTG in major depression., Methods: We used the baseline data of the METADAP cohort, comprising 624 patients with a current MDE in a context of Major Depressive Disorder treated in psychiatry settings, without current alcohol use disorders. Patients were screened for severe insomnia, defined by a score of four or more on the three Hamilton Depression Rating Scale (HDRS) sleep items, and for HTG characterised by TG≥200mg/dL., Results: Severe insomnia was observed in 335(54%) patients with a current MDE, of whom 234(70%) were women; 49(8%) patients had HTG, of whom 25(51%) were women. 69(11%) patients were treated with lipid-lowering drugs. Severe insomnia was associated with a higher frequency of HTG in the whole sample (9.9% vs 5.6%, p=0.046) and in the subgroup of women (9.0% vs 2.0%, p=0.002). Multivariate logistic regression analyses adjusted for age, education levels, BMI and total HDRS scores confirmed the association between severe insomnia and HTG in the whole sample (OR=2.02, 95%CI [1.00-4.08], p=0.05) as well as in the subgroup of women (OR=4.82, 95%CI [1.5-15.5], p=0.008). No association was shown in men., Perspectives: HTG should be systematically investigated in depressed patients with severe insomnia and particularly in women. Further studies are needed to explain the association we observed between severe insomnia and HTG., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Neural substrates of bipolar disorder (BD) have frequently been characterized by dysregulation of fronto-limbic networks that may persist during euthymic periods. Only a few studies have investigated euthymic bipolar patients (BP) functional connectivity at rest. The current study aims to assess resting-state functional connectivity in euthymic BP in order to identify trait abnormalities responsible for enduring mood dysregulation in these patients., Methods: Medial prefrontal cortex (mPFC) functional connectivity was investigated in 20 euthymic BP and 20 healthy subjects (HS). The functional connectivity maps were compared across groups using a between-group random effect analysis. Additional region of interest (ROI) analysis focused on mPFC-amygdala functional connectivity as well as correlations between the clinical features in euthymic BP was also conducted., Results: A significant difference between euthymic BP and HS was observed in terms of connectivity between the mPFC and the right dorsolateral prefrontal cortex (dlPFC). A significant negative correlation between the activity of these regions was found in HS but not in euthymic BP. In addition, euthymic BP showed greater connectivity between mPFC and right amygdala compared to HS, which was also correlated with the duration of the disease., Limitations: The BP group was heterogeneous with respect to the bipolarity subtype and the medication. The robustness of results could be improved with an increased sample size., Conclusions: Compared to HS, the euthymic BP showed abnormal decoupling (decreased functional connectivity) activity between mPFC-dlPFC and hyperconnectivity (increased functional connectivity) and between mPFC and amygdala. These abnormalities could underlie the pathophysiology of BD, and may deteriorate further in accordance with disease duration., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Bipolar disorders (BD) are mainly characterized by emotional and cognitive processing impairment. The cerebral substrate explaining BD impairment and the action mechanisms of therapies are not completely understood, especially for psychosocial interventions. This fMRI study aims at assessing cerebral correlates of euthymic bipolar patients (EBP) before and after psychoeducation therapy. Sixteen EBP and 16 matched healthy subjects (HS) performed a word-face emotional Stroop task in two separate fMRI sessions at 3-month interval. Between fMRI sessions, EBP underwent psychoeducation. Before psychoeducation, the comparison of EBP vs. HS in fMRI data revealed (a) significant decreased activity of cognitive control regions such as bilateral inferior and left superior frontal gyri, right insula, right fusiform gyrus and bilateral occipital gyri and (b) significant increased activity of emotion-related processing regions such as bilateral hippocampus, parahippocampal gyri and the left middle temporal gyrus. After psychoeducation, EBP showed significant clinical improvement, increased activity of inferior frontal gyri and a tendency toward decreased activity of right hippocampus and parahippocampal gyrus. These results suggest that the imbalance between cognitive control and emotion processing systems characterizing BD acute episodes may persist during euthymic periods. Moreover, this imbalance may be improved by psychoeducation, which enhances the cognitive control and modulates emotional fluctuations in EBP., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Eight patients with major depression, included in a double-blind study, performed an antisaccade task. Results suggested a link between antisaccade performances and clinical scale scores in patients who respond to therapy. Moreover, error rates may well predict response from day of inclusion, thus serving as a state-marker for mood disorders., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The Clinical Global Impression scale (CGI) is frequently used in clinical research because of its face validity and ease of use but data on its reliability are scarce. Our goal was to estimate the reliability of the scale and compare reliability between face-to-face and video scoring. We analyzed 50 different video interviews recorded during 5 visits of a crossover trial to study the effect of subthalamic nucleus stimulation. Six specialized clinicians rated the CGI using these videos, providing 300 different ratings. The intraclass correlation was lower at inclusion (0.30 [0.13-0.50]) than at later visits (0.68 [0.61-0.80]). Reliability was not influenced by the patients' stimulation status. The mean of at least two independent evaluations of the video is needed to achieve an ICC greater than 0.8. The video CGI is a valid clinical outcome measure suitable for clinical trials (ClinicalTrials.gov number, NCT00169377)., (Copyright © 2010 Elsevier Ltd. All rights reserved.)