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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.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).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.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.

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.

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, Hopitaux 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, Severine Trabado, Albane Vievard, Celine Verstuyft, Romain Colle and Emmanuelle Corruble have nothing to declare.

International audience; 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

International audience; 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

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.

International audience; BackgroundNeural 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.MethodsMedial 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.ResultsA 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.LimitationsThe 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.ConclusionsCompared 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.