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1. Intervenir précocement dans les stades débutants du trouble bipolaire : pourquoi, quand et comment

Author: Philippe Conus, M Rigon, Clément Dondé, Frédéric Haesebaert, Arnaud Pouchon, Mircea Polosan, E. Fakra, G Legrand, E Schmitt, and Thierry Bougerol
Subjects: Gynecology, First episode, Psychiatry and Mental health, Health services, medicine.medical_specialty, Arts and Humanities (miscellaneous), business.industry, medicine, business
Abstract: Resume Objectifs Le developpement d’une politique d’intervention precoce des les stades debutants du trouble bipolaire (TB), c’est-a-dire les symptomes d’etat a risque de TB et le premier episode maniaque/hypomaniaque, represente un enjeu crucial pour optimiser le pronostic des personnes concernees. Methode Revue narrative de litterature sur le sujet de l’intervention precoce chez les sujets presentant un stade debutant de TB, incluant une premiere partie sur les facteurs de risque et les caracteristiques cliniques, une seconde sur les outils utilises pour le depistage precoce, et une troisieme sur les approches therapeutiques de ces stades debutants. Resultats Le clinicien doit s’appuyer sur la connaissance des facteurs de risque de TB et sur une semeiologie specifique des stades debutants. Il existe des outils et des criteres permettent un depistage precoce chez certaines populations a risque qui doivent faire l’objet d’une attention particuliere, comme les enfants de personnes vivant avec un TB. Les traitements pharmacologiques restent essentiellement symptomatiques pour les symptomes d’etat a risque, tandis que les stabilisateurs de l’humeur non antipsychotique en monotherapie doivent etre preferes pour le premier episode maniaque/hypomaniaque. Certaines approches non-pharmacologiques comme la psychoeducation, la psychotherapie et la rehabilitation ont prouve leur efficacite dans les stades debutants de TB. Conclusions Les dispositifs d’intervention precoce deja en place pour les stades debutant de psychose auraient toute legitimite a inclure des personnes concernees par un stade debutant de TB. Le developpement futur de recommandations specifiques sera indispensable pour structurer cette offre de soin.
Published: 2022
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2. Pharmacological treatment profiles in the FACE-BD cohort: An unsupervised machine learning study, applied to a nationwide bipolar cohort✰

Author: Emilie Olié, Sébastien Brodeur, Chantal Henry, Jean-Luc Bosson, Paul Roux, Emmanuel Haffen, Bruno Aouizerate, Thierry Bougerol, Sébastien Gard, Hugo Terrisse, Frank Bellivier, Ludovic Samalin, Ophélia Godin, Raoul Belzeaux, Arnaud Pouchon, Caroline Dubertret, Raymund Schwan, Valerie Aubin, Bruno Etain, Marion Leboyer, Philippe Courtet, Mircea Polosan, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Louis Mourier - AP-HP [Colombes], Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Centre Hospitalier Universitaire [Grenoble] (CHU), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Bordeaux [Bordeaux], Centre Hospitalier Princesse Grace, Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Centre Hospitalier de Versailles André Mignot (CHV), CHU Clermont-Ferrand, and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: medicine.medical_specialty, Longitudinal study, Bipolar Disorder, Lithium (medication), [SDV]Life Sciences [q-bio], Disease, Lamotrigine, Pharmacological treatment, 03 medical and health sciences, 0302 clinical medicine, Antimanic Agents, Mood stabilizers, Internal medicine, medicine, Humans, Functioning, Longitudinal Studies, Bipolar disorder, ComputingMilieux_MISCELLANEOUS, Maintenance treatment, business.industry, Valproic Acid, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Mood, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, 030217 neurology & neurosurgery, Unsupervised Machine Learning, medicine.drug
Abstract: 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.
Published: 2021
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3. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

Author: Thomas Frodl, Eduard Vieta, Sean N. Hatton, Sophia I. Thomopoulos, Jens Sommer, Fábio L.S. Duran, Pauline Favre, Cynthia H.Y. Fu, Tony T. Yang, Knut Schnell, Tilo Kircher, Gloria Roberts, Lyubomir I. Aftanas, Norbert Hosten, Elena Pozzi, Henrik Walter, Pedro G.P. Rosa, Oliver Gruber, Colm G. Connolly, Klaus Berger, Jonathan Repple, Geraldo Busatto Filho, Tomas Hajek, Bernd Kramer, Salvador Sarró, Ulrik Fredrik Malt, Richard Dinga, Danai Dima, Mikael Landén, Laura K.M. Han, Jonathan Savitz, Peter R. Schofield, Axel Krug, Maria M. Rive, Caterina del Mar Bonnín, Edith Pomarol-Clotet, Olaf Steinsträter, Chantal Henry, Udo Dannlowski, Henricus G. Ruhé, Mauricio H. Serpa, Quinn McLellan, Benson Mwangi, Philipp G. Saemann, Christopher G. Davey, Marie-José van Tol, Mircea Polosan, Torbjørn Elvsåshagen, Nynke A. Groenewold, Marcus V. Zanetti, Claas Kähler, Jair C. Soares, Steven J.A. van der Werff, Kathryn R. Cullen, Lachlan T. Strike, Ilya M. Veer, Beata R. Godlewska, Giovana Zunta-Soares, Xavier Caseras, Janice M. Fullerton, Bronwyn Overs, Tiffany M. Chaim-Avancini, Lisa T. Eyler, Theodore D. Satterthwaite, Martin Ingvar, Ramona Leenings, Angela Carballedo, Brenda W.J.H. Penninx, Ian B. Hickie, James H. Cole, Elena Filimonova, Márcio Gerhardt Soeiro-de-Souza, Rayus Kuplicki, Leila Nabulsi, Ben J. Harrison, Aart H. Schene, Ivan V. Brak, Nic J.A. van der Wee, Hans J. Grabe, Katharina Wittfeld, Anouk Schrantee, Matthew D. Sacchet, Margaret J. Wright, Dan J. Stein, Erlend Bøen, Heather C. Whalley, Egle Simulionyte, Fleur M. Howells, Tim Hahn, Lianne Schmaal, Garrett M. Timmons, Bartholomeus C M Haarman, Kang Sim, Andrew M. McIntosh, Moji Aghajani, Jim Lagopoulos, Anne Uhlmann, Rodrigo Machado-Vieira, Jose Manuel Goikolea, Mon-Ju Wu, Christopher R.K. Ching, Dara M. Cannon, Liesbeth Reneman, Andreas Jansen, Josselin Houenou, Ian H. Gotlib, Bonnie Klimes-Dougan, Raymond Salvador, Maria J. Portella, Ole A. Andreassen, Greig I. de Zubicaray, Robert Vermeiren, Bryon A. Mueller, Nils R. Winter, Dick J. Veltman, Neda Jahanshad, Stefan Frenzel, Philip B. Mitchell, Colm McDonald, Henry Völzke, Daniel H. Wolf, Katie L. McMahon, Evgeny Osipov, Marco Hermesdorf, Tiffany C. Ho, Bernhard T. Baune, Paul M. Thompson, Glenda MacQueen, Andre F. Marquand, Maria Concepcion Garcia Otaduy, Vasileios Zannias, Christoph Abé, Ashley N. Sutherland, Sarah E. Medland, Beny Lafer, Erick J. Canales-Rodríguez, Geoffrey B. Hall, Martin Alda, Henk Temmingh, Sonya Foley, Verena Enneking, Frank P. MacMaster, Dominik Grotegerd, Joaquim Radua, Baptiste Couvy-Duchesne, André Aleman, Radiology and Nuclear Medicine, ANS - Brain Imaging, ANS - Compulsivity, Impulsivity & Attention, APH - Personalized Medicine, APH - Mental Health, Ontwikkelingspsychologie (Psychologie, FMG), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Clinical Neuropsychology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Radiology and nuclear medicine, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Complex Trait Genetics, and APH - Digital Health
Subjects: Adult, Male, medicine.medical_specialty, Aging, Adolescent, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], BF, Health outcomes, Article, Cellular and Molecular Neuroscience, 03 medical and health sciences, Lateral ventricles, Young Adult, 0302 clinical medicine, Atrophy, Internal medicine, medicine, Humans, ddc:610, Longitudinal Studies, Molecular Biology, diagnostic imaging [Brain], Brain aging, Depression (differential diagnoses), 030304 developmental biology, Aged, 0303 health sciences, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Depression, 220 Statistical Imaging Neuroscience, Brain, Chronological age, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, Psychiatry and Mental health, Increased risk, RC0321, Major depressive disorder, Female, Age of onset, business, 030217 neurology & neurosurgery, Neuroscience
Abstract: BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset.MethodsWe performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain predicted age difference (brain-PAD).FindingsOn average, MDD patients showed a higher brain-PAD of +0.90 (SE 0.21) years (Cohen’s d=0.12, 95% CI 0.06-0.17) compared to controls. Relative to controls, first-episode and currently depressed patients showed higher brain-PAD (+1.2 [0.3] years), and the largest effect was observed in those with late-onset depression (+1.7 [0.7] years). In addition, higher brain-PAD was associated with higher self-reported depressive symptomatology (b=0.05, p=0.004).InterpretationThis highly powered collaborative effort showed subtle patterns of abnormal structural brain aging in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the predictive value of these brain-PAD estimates.FundingThis work was supported, in part, by NIH grants U54 EB020403 and R01 MH116147.
Published: 2021
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4. Violent suicide attempt history in elderly patients with bipolar disorder: The role of sex, abdominal obesity, and verbal memory: Results from the FACE-BD cohort (FondaMental Advanced center of Expertise for Bipolar Disorders)

Author: Raoul Belzeaux, Mircea Polosan, Aiste Lengvenyte, Paul Roux, Joséphine Loftus, Sébastien Gard, Christine Passerieux, Emeline Marlinge, Emmanuel Haffen, Emilie Olié, Valerie Aubin, Bruno Aouizerate, Caroline Dubertret, Raymund Schwan, Bruno Etain, Philippe Courtet, Pierre-Michel Llorca, Marion Leboyer, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Fondation FondaMental [Créteil], Vilnius University [Vilnius], Centre hospitalier Charles Perrens [Bordeaux], Hôpital Princesse Grace [Monaco], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Louis Mourier - AP-HP [Colombes], Université Paris Cité (UPCité), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier de Versailles André Mignot (CHV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported (in part) by the Fondation FondaMental, Créteil, France and by the Investissements d'Avenir programs managed by the ANR under references ANR-11- IDEX-0004-02 and ANR-10-COHO-10-01, Hôpital Charles Perrens, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Université Paris-Saclay, Guerineau, Nathalie C., and Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: Male, Bipolar disorder, [SDV]Life Sciences [q-bio], Suicide, Attempted, 03 medical and health sciences, 0302 clinical medicine, Memory, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Obesity, Abdominal obesity, Aged, Retrospective Studies, California Verbal Learning Test, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Suicide attempt, business.industry, Cohort, Cognition, Middle Aged, medicine.disease, Middle age, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Suicide, Cross-Sectional Studies, Obesity, Abdominal, Quantitative Biology - Neurons and Cognition, FOS: Biological sciences, Female, Neurons and Cognition (q-bio.NC), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cognitive function, medicine.symptom, Verbal memory, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Clinical psychology
Abstract: International audience; 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.
Published: 2022
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5. tDCS as a first-choice agent in individuals at high-risk for psychosis?

Author: Clément Dondé, Jerome Brunelin, Arnaud Pouchon, and Mircea Polosan
Subjects: Psychiatric Status Rating Scales, Psychosis, medicine.medical_specialty, Transcranial direct-current stimulation, business.industry, medicine.medical_treatment, At risk mental state, Ultra high risk, Transcranial Direct Current Stimulation, medicine.disease, Psychiatry and Mental health, Psychotic Disorders, Arts and Humanities (miscellaneous), medicine, Humans, business, Psychiatry
Published: 2022
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6. The Effects of Transcranial Electrical Stimulation of the Brain on Sleep: A Systematic Review

Author: Clément Dondé, Jerome Brunelin, Jean-Arthur Micoulaud-Franchi, Julia Maruani, Michel Lejoyeux, Mircea Polosan, Pierre A. Geoffroy, Brunelin, Jérôme, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Psychiatric Disorders, Neuroscience Research and Clinical Research (PSYR2), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], CHU Bordeaux [Bordeaux], Sommeil, Addiction et Neuropsychiatrie [Bordeaux] (SANPSY), Université de Bordeaux (UB)-CHU de Bordeaux Pellegrin [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris Diderot - Paris 7 (UPD7), and Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141))
Subjects: medicine.medical_specialty, subjective sleep, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, RC435-571, Polysomnography, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, systematic review, medicine, sleep, 030304 developmental biology, Psychiatry, 0303 health sciences, medicine.diagnostic_test, business.industry, transcranial electrical stimulation, food and beverages, Sleep in non-human animals, Clinical Practice, Sleep patterns, Psychiatry and Mental health, sleep pattern, systematic review Literature Search Strategy, sleep oscillations, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Subjective sleep, business, 030217 neurology & neurosurgery, Electrical brain stimulation
Abstract: International audience; Transcranial Electrical Stimulation (tES) is a promising non-invasive brain modulation tool. Over the past years, there have been several attempts to modulate sleep with tES-based approaches in both the healthy and pathological brains. However, data about the impact on measurable aspects of sleep remain scattered between studies, which prevent us from drawing firm conclusions. We conducted a systematic review of studies that explored the impact of tES on neurophysiological sleep oscillations, sleep patterns measured objectively with polysomnography, and subjective psychometric assessments of sleep in both healthy and clinical samples. We searched four main electronic databases to identify studies until February 2020. Forty studies were selected including 511 healthy participants and 452 patients. tES can modify endogenous brain oscillations during sleep. Results concerning changes in sleep patterns are conflicting, whereas subjective assessments show clear improvements after tES. Possible stimulation-induced mechanisms within specific cortico-subcortical sleep structures and networks are discussed. Although these findings cannot be directly transferred to the clinical practice and sleep-enhancing devices development for healthy populations, they might help to pave the way for future researches in these areas. PROSPERO registration number 178910.
Published: 2021
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7. Pharmacological treatment profiles in the FACE-BD cohort: Treatment description and complete data for bipolar subtypes

Author: Bruno Aouizerate, Ludovic Samalin, Ophélia Godin, Thierry Bougerol, Raoul Belzeaux, Sébastien Brodeur, Valerie Aubin, Jean-Luc Bosson, Emilie Olié, Frank Bellivier, Bruno Etain, Sébastien Gard, Emmanuel Haffen, Arnaud Pouchon, Caroline Dubertret, Raymund Schwan, Mircea Polosan, Hugo Terrisse, Chantal Henry, Philippe Courtet, Paul Roux, Marion Leboyer, Centre Hospitalier Universitaire [Grenoble] (CHU), Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-ThEMAS ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Fondation FondaMental [Créteil], Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Princesse Grace [Monaco], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), CHU Bordeaux [Bordeaux], UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier de Versailles André Mignot (CHV), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), and haffen, emmanuel
Subjects: Hierarchical agglomerative clustering, Complete data, medicine.medical_specialty, Science (General), Data set, Macine learning, [SDV]Life Sciences [q-bio], Computer applications to medicine. Medical informatics, R858-859.7, Pharmacological treatment, Clusters, 03 medical and health sciences, Q1-390, 0302 clinical medicine, Internal medicine, Machine learning, Bipolar disorders, Medicine, Data Article, 030304 developmental biology, 0303 health sciences, Multidisciplinary, business.industry, [SDV] Life Sciences [q-bio], Pharmacological interventions, Cohort, business, Clinical evaluation, 030217 neurology & neurosurgery, Cohort study
Abstract: International audience; In the current study, we provide the list of pharmacological interventions applied during the one-year follow-up period of the Pharmacological treatment profiles in the FACE-BD cohort study. These data show the treatments used in the new clusters formed in this previous study and also in usual bipolarity subtypes. The proportion of each treatment used during the follow-up was calculated. Days on each treatment were also included in this dataset. The complete clinical and paraclinical data analyzed for clusters and bipolar subtypes were included in this dataset. Socio-demographic self-administered and clinician-administered scales, clinical evaluation during the follow-up, psychiatric and somatic comorbidities, and blood tests are shown in this material.
Published: 2021
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8. Pitolisant for Treating Narcolepsy Comorbid With Schizophrenia

Author: Clément Dondé, Mircea Polosan, and Rita Guzun
Subjects: medicine.medical_specialty, Pitolisant, business.industry, Treatment outcome, MEDLINE, medicine.disease, Comorbidity, Psychiatry and Mental health, chemistry.chemical_compound, chemistry, Schizophrenia, Schizophrenic Psychology, medicine, Pharmacology (medical), Young adult, Psychiatry, business, Narcolepsy
Published: 2020
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9. Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study

Author: Morgane Péré, Mircea Polosan, Sylvain Harquel, Jerome Brunelin, Thierry Bougerol, David Szekely, Gaelle Dall’Igna, Christian Marendaz, Samuel Bulteau, Jean-Marie Vanelle, Lysianne Beynel, Anne Sauvaget, Nathalie Guyader, Alan Chauvin, Service d'addictologie[CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), IRMaGe (IRMaGe ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), GIPSA - Vision and Brain Signal Processing (GIPSA-VIBS), Département Images et Signal (GIPSA-DIS), Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Psychiatrie, CHU Grenoble, Fondation FondaMental [Créteil], Schizophrenies Débutantes et Résistantes : de la Physiopathologie à la Thérapeutique, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Clinique de psychiatrie, CCSD, Accord Elsevier, and Centre Hospitalier Universitaire [Grenoble] (CHU)
Subjects: Adult, Male, Bipolar Disorder, Prefrontal Cortex, Pilot Projects, Stimulation, Controlled studies, 050105 experimental psychology, Depressive Disorder, Treatment-Resistant, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Humans, Medicine, 0501 psychology and cognitive sciences, Adverse effect, ComputingMilieux_MISCELLANEOUS, Depression (differential diagnoses), Depressive Disorder, Major, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, 05 social sciences, Significant difference, General Medicine, Transcranial Magnetic Stimulation, 3. Good health, Dorsolateral prefrontal cortex, Theta burst, Treatment Outcome, medicine.anatomical_structure, Neurology, Tolerability, Anesthesia, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: The safety and efficacy of neuronavigated intermittent theta burst stimulation (iTBS) in patients with bipolar depression has not yet been investigated. We hypothesized the superiority of active iTBS over sham. Twenty-six patients were randomly allocated to receive either active (n=12) or sham (n=14) iTBS. Response and remission rates according to changes in depression MADRS score were high following active iTBS (72% and 42% for response and remission rates, respectively), but no significant difference was found after sham stimulation (42%and 25%). No adverse events were observed. This study revealed the safety and tolerability of twice daily iTBS in patients with bipolar depression. Larger controlled studies are warranted to prove iTBS superiority in treatment-resistant bipolar depression.
Published: 2019
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10. Cerebellar parcellation in schizophrenia and bipolar disorder

Author: Charles Laidi, Mary L. Phillips, Jean-François Mangin, Marion Leboyer, Mircea Polosan, Julia Linke, José V. Manjón, Franz Hozer, Paolo Brambilla, Josselin Houenou, José E. Romero, Amelia Versace, Michèle Wessa, Marian Kolenic, Samuel Sarrazin, Filip Spaniel, Pierrick Coupé, Tomas Hajek, Pauline Favre, Edouard Duchesnay, Marc-Antoine d'Albis, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Psychiatrie et Neurologie personnalisées [AP-HP Hôpital Henri-Mondor] (DHU PePsy), Hôpital Henri Mondor, Fondation FondaMental [Créteil], Dalhousie University [Halifax], National Institute of Mental Health [Klecany, Czech Republic] (NIMH), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University Medical Center of the Johannes Gutenberg-University Mainz, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Universitat Politècnica de València (UPV), Hôpital Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), and Coupé, Pierrick
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Cerebellum, Bipolar Disorder, cerebellum, Lithium (medication), [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Cerebellar Gray Matter, Cerebellar Cortex, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Antimanic Agents, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Medicine, Bipolar disorder, business.industry, segmentation, Cognition, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, Psychiatry and Mental health, medicine.anatomical_structure, nervous system, Multicenter study, lithium, Schizophrenia, parcellation, Lithium Compounds, Female, business, 030217 neurology & neurosurgery, medicine.drug, Schizophrenia spectrum
Abstract: International audience; Objective: The cerebellum is involved in cognitive processing and emotion control. Cerebellar alterations could explain symptoms of schizophrenia spectrum disorder (SZ) and bipolar disorder (BD). In addition, literature suggests that lithium might influence cerebellar anatomy. Our aim was to study cerebellar anatomy in SZ and BD, and investigate the effect of lithium.Methods: Participants from 7 centers worldwide underwent a 3T MRI. We included 182 patients with SZ, 144 patients with BD, and 322 controls. We automatically segmented the cerebellum using the CERES pipeline. All outputs were visually inspected.Results: Patients with SZ showed a smaller global cerebellar gray matter volume compared to controls, with most of the changes located to the cognitive part of the cerebellum (Crus II and lobule VIIb). This decrease was present in the subgroup of patients with recent-onset SZ. We did not find any alterations in the cerebellum in patients with BD. However, patients medicated with lithium had a larger size of the anterior cerebellum, compared to patients not treated with lithium.Conclusion: Our multicenter study supports a distinct pattern of cerebellar alterations in SZ and BD.
Published: 2019
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11. Early weight gain predicts later metabolic syndrome in depressed patients treated with antidepressants: Findings from the METADAP cohort

Author: Khalil El Asmar, Céline Verstuyft, Bruno Fève, Emmanuel Haffen, Mircea Polosan, Emmanuelle Corruble, Bruno Falissard, Florian Ferreri, Séverine Trabado, Florence Gressier, Philippe Chanson, Romain Colle, Laurent Becquemont, and Albane Vievard
Subjects: Adult, Male, medicine.medical_specialty, Waist, Comorbidity, Weight Gain, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Major depressive episode, Biological Psychiatry, Metabolic Syndrome, Depressive Disorder, Major, business.industry, Incidence, Incidence (epidemiology), Hypertriglyceridemia, Middle Aged, Prognosis, medicine.disease, Antidepressive Agents, 030227 psychiatry, Psychiatry and Mental health, Cohort, Major depressive disorder, Female, medicine.symptom, Metabolic syndrome, business, Weight gain, 030217 neurology & neurosurgery
Abstract: Background Metabolic syndrome (MetS) is a major public health issue. We assessed whether early weight gain predicts later MetS in depressed patients treated with antidepressants. Methods In the 6-month prospective METADAP cohort, 260 non-overweight patients with a Major Depressive Disorder (MDD) and a current Major Depressive Episode (MDE) were assessed for early weight gain (>5%) after one month of treatment, and for the later incidence of MetS after three and six months of treatment. Outcome variables were MetS, the number of MetS criteria, and each MetS criterion (high Waist Circumference (WC), high Blood Pressure (BP), high triglyceridemia (TG), low HDL-Cholesterolemia, and high Fasting Plasma Glucose (FPG). Multivariate models were adjusted for age, sex, previous MDD duration, severity of current MDE, and antidepressants. Results 24.6% of patients had early weight gain. Compared to those without weight gain, patients with early weight gain had higher MetS incidence: 16.7% vs. 6.9% after 3 months (p = 0.07), and 23.8% vs. 7.1% after 6 months (p = 0.02). Among completers (n = 120), early weight gain was significantly associated with later MetS incidence (OR: 5.5) and a higher number of MetS criteria (IRR: 1.7). This effect was driven by the WC, TG, and HDL-C criteria. Conclusion Compared to Non-early weight gainers, patients with early weight gain in the first month of antidepressant treatment have a significant higher risk of developing MetS during the 6 months of treatment. Early weight monitoring is recommended in order to set preventive measures to avoid new metabolic syndromes in depressed patients treated with antidepressants.
Published: 2018
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12. Early weight gain predicts later weight gain in depressed patients treated with antidepressants: Findings from the METADAP cohort

Author: Mircea Polosan, Florian Ferreri, Emmanuelle Corruble, Séverine Trabado, Philippe Chanson, Khalil El Asmar, Albane Vievard, Laurent Becquemont, Bruno Falissard, Romain Colle, Bruno Fève, Emmanuel Haffen, Céline Verstuyft, and Florence Gressier
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Weight Gain, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Prospective Studies, Major depressive episode, Prospective cohort study, Aged, Depressive Disorder, Major, Weight monitoring, business.industry, Middle Aged, Overweight, Antidepressive Agents, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Family member, ROC Curve, Area Under Curve, Cohort, Female, medicine.symptom, business, Weight gain, Bristol-Myers, 030217 neurology & neurosurgery, Cohort study
Abstract: 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.
Published: 2018
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13. Punding Behavior as a Red Flag for Dementia in a Patient With Depression: Case Report

Author: Mircea Polosan, Clément Dondé, and Arnaud Pouchon
Subjects: Pediatrics, medicine.medical_specialty, lcsh:RC435-571, Case Report, mood disorder, abnormal movement, frontotemporal dementia, 03 medical and health sciences, 0302 clinical medicine, lcsh:Psychiatry, Punding, medicine, Dementia, brain perfusion SPECT, Depression (differential diagnoses), 030304 developmental biology, Psychiatry, 0303 health sciences, medicine.diagnostic_test, business.industry, Lumbar puncture, Neuropsychology, medicine.disease, punding, Subthalamic nucleus, Psychiatry and Mental health, depression, Major depressive disorder, business, 030217 neurology & neurosurgery, dementia, Frontotemporal dementia
Abstract: Punding is defined as a stereotypic, complex, repetitive, and non-goal-oriented activity. This behavior has been observed in Parkinson's disease and chronic amphetamine users. However, in general, punding behavior is largely under-diagnosed. Here, we describe a rare case of a 53-year-old woman showing punding behavior during major depressive disorder with atypical clinical features suggestive of a frontal syndrome. Neuropsychological evaluations mainly reported deficits in executive functioning. Brain MRI and lumbar puncture were normal. Brain perfusion SPECT showed hypoperfusion predominating in the right frontal and parietooccipital lobes, and a slight hypoperfusion in subthalamic nucleus including the posterior area of right striatum. We diagnosed this case as a frontotemporal dementia. Punding behavior could be a red flag for dementia in patients with major depressive disorder.
Published: 2021
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14. Characterization of depressed bipolar patients with current suicidal ideation

Author: Pierre-Michel Llorca, Bruno Etain, Christine Passerieux, Marion Leboyer, Mircea Polosan, Paul Roux, Bénédicte Nobile, Valerie Aubin, Sébastien Gard, Emmanuel Haffen, Raoul Belzeaux, Caroline Dubertret, Raymund Schwan, Frank Bellivier, Emilie Olié, Bruno Aouizerate, Joséphine Loftus, Jonathan Dubois, Philippe Courtet, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fondation FondaMental [Créteil], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Charles Perrens, Hôpital Princesse Grace [Monaco], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), CHU Clermont-Ferrand, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier de Versailles André Mignot (CHV), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Centre hospitalier Charles Perrens [Bordeaux], and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC)
Subjects: medicine.medical_specialty, Bipolar disorder, [SDV]Life Sciences [q-bio], Suicide, Attempted, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Suicidal patients, Prospective cohort study, Psychiatry, Suicidal ideation, Depression (differential diagnoses), Psychiatric Status Rating Scales, Depressive Disorder, business.industry, General Medicine, medicine.disease, 3. Good health, 030227 psychiatry, suicidal ideation, Psychiatry and Mental health, depression, Self Report, medicine.symptom, Attempt suicide, business, 030217 neurology & neurosurgery, prospective study
Abstract: Objective: Bipolar disorder is one of the most frequent psychiatric disorders among suicidal patients. A large part of patients with bipolar disorder (30–50%) will attempt suicide. Suicidal ideation being a major risk factor of suicidal act, it is crucial to better characterize patients with suicidal bipolar depression (i.e. depression with current suicidal ideation). The aim of this study was to characterize suicidal bipolar depressed patients in comparison with non-suicidal depressed patients in terms of clinical characteristics, evolution of depression and suicidal ideation course over time, and risk of suicide attempt during follow-up. Methods: Among patients with bipolar disorder recruited from the network of FondaMental expert centres for bipolar disorder between 2009 and 2017, we selected patients with at least mild depression (Montgomery–Åsberg Depression Rating Scale total score >11) and without current manic symptomatology (Young Mania Rating Scale total score Results: Baseline clinical features (e.g. depression severity, childhood trauma, global functioning) were more severe in patients with than without suicidal depression. Suicidal patients tended to remain more suicidal throughout the follow-up than patients without suicidal ideation at baseline (3.4-fold higher risk of persistent suicidal ideation at the 2-year visit despite an improvement in depressive symptomatology). Conclusions: Depressed bipolar disorder patients reporting suicidal ideation had more severe clinical features at baseline and were more prone to report persistent suicidal ideation during the follow-up, independently of thymic state. Clinicians should closely monitor this subgroup of patients.
Published: 2021
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15. A Unified Functional Network Target for Deep Brain Stimulation in Obsessive-Compulsive Disorder

Author: Bassam Al-Fatly, Harith Akram, Svenja Treu, Andrea A. Kühn, Ningfei Li, Stephan Chabardes, Bryan A. Strange, Veerle Visser-Vandewalle, Mircea Polosan, Astrid Kibleur, Jens H. Kuhn, Juan A. Barcia, Juan Carlos Baldermann, Andreas Horn, Ludvic Zrinzo, Barbara Hollunder, and Eileen M. Joyce
Subjects: 0301 basic medicine, Obsessive-Compulsive Disorder, Deep brain stimulation, medicine.medical_treatment, Deep Brain Stimulation, Precuneus, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Internal Capsule, Subthalamic Nucleus, Medicine, Humans, Biological Psychiatry, Anterior cingulate cortex, medicine.diagnostic_test, business.industry, Magnetic Resonance Imaging, Subthalamic nucleus, 030104 developmental biology, medicine.anatomical_structure, Superior frontal gyrus, Connectome, business, Functional magnetic resonance imaging, Insula, Neuroscience, 030217 neurology & neurosurgery
Abstract: Background Multiple deep brain stimulation (DBS) targets have been proposed for treating intractable obsessive-compulsive disorder (OCD). Here, we investigated whether stimulation effects of different target sites would be mediated by one common or several segregated functional brain networks. Methods First, seeding from active electrodes of 4 OCD patient cohorts (N = 50) receiving DBS to anterior limb of the internal capsule or subthalamic nucleus zones, optimal functional connectivity profiles for maximal Yale-Brown Obsessive Compulsive Scale improvements were calculated and cross-validated in leave-one-cohort-out and leave-one-patient-out designs. Second, we derived optimal target-specific connectivity patterns to determine brain regions mutually predictive of clinical outcome for both targets and others predictive for either target alone. Functional connectivity was defined using resting-state functional magnetic resonance imaging data acquired in 1000 healthy participants. Results While optimal functional connectivity profiles showed both commonalities and differences between target sites, robust cross-predictions of clinical improvements across OCD cohorts and targets suggested a shared network. Connectivity to the anterior cingulate cortex, insula, and precuneus, among other regions, was predictive regardless of stimulation target. Regions with maximal connectivity to these commonly predictive areas included the insula, superior frontal gyrus, anterior cingulate cortex, and anterior thalamus, as well as the original stereotactic targets. Conclusions Pinpointing the network modulated by DBS for OCD from different target sites identified a set of brain regions to which DBS electrodes associated with optimal outcomes were functionally connected—regardless of target choice. On these grounds, we establish potential brain areas that could prospectively inform additional or alternative neuromodulation targets for obsessive-compulsive disorder.
Published: 2021

16. Contrastive Learning with Continuous Proxy Meta-data for 3D MRI Classification

Author: Michèle Wessa, Julie Victor, Mary L. Phillips, Camille Piguet, Pauline Favre, Benoit Dufumier, Antoine Grigis, Lisa T. Eyler, Paolo Brambilla, Colm McDonald, Pietro Gori, Edouard Duchesnay, and Mircea Polosan
Subjects: Matching (statistics), Artificial neural network, business.industry, Computer science, Supervised learning, Machine learning, computer.software_genre, Metadata, Discriminative model, Leverage (statistics), Artificial intelligence, Proxy (statistics), business, Representation (mathematics), computer
Abstract: Traditional supervised learning with deep neural networks requires a tremendous amount of labelled data to converge to a good solution. For 3D medical images, it is often impractical to build a large homogeneous annotated dataset for a specific pathology. Self-supervised methods offer a new way to learn a representation of the images in an unsupervised manner with a neural network. In particular, contrastive learning has shown great promises by (almost) matching the performance of fully-supervised CNN on vision tasks. Nonetheless, this method does not take advantage of available meta-data, such as participant’s age, viewed as prior knowledge. Here, we propose to leverage continuous proxy metadata, in the contrastive learning framework, by introducing a new loss called y-Aware InfoNCE loss. Specifically, we improve the positive sampling during pre-training by adding more positive examples with similar proxy meta-data with the anchor, assuming they share similar discriminative semantic features. With our method, a 3D CNN model pre-trained on \(10^4\) multi-site healthy brain MRI scans can extract relevant features for three classification tasks: schizophrenia, bipolar diagnosis and Alzheimer’s detection. When fine-tuned, it also outperforms 3D CNN trained from scratch on these tasks, as well as state-of-the-art self-supervised methods. Our code is made publicly available here.
Published: 2021
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17. Non‐alcoholic fatty liver disease in a sample of individuals with bipolar disorders: results from the FACE‐BD cohort

Author: Ophelia, Godin, Marion, Leboyer, Raoul, Belzeaux, Frank, Bellivier, Joséphine, Loftus, Philippe, Courtet, Caroline, Dubertret, Sebastien, Gard, Chantal, Henry, Pierre-Michel, Llorca, Raymund, Schwan, Christine, Passerieux, Mircea, Polosan, Ludovic, Samalin, Emilie, Olié, Bruno, Etain, A, Bing, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Male, medicine.medical_specialty, Bipolar Disorder, liver diseases, [SDV]Life Sciences [q-bio], Population, Disease, Overweight, Cohort Studies, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Risk Factors, Internal medicine, medicine, Prevalence, Humans, education, ComputingMilieux_MISCELLANEOUS, Aged, Metabolic Syndrome, education.field_of_study, business.industry, Fatty liver, nutritional and metabolic diseases, medicine.disease, Obesity, digestive system diseases, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Alcoholism, psychiatric disorders, Cohort, fatty liver disease, Female, metabolic abnormalities, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, Metabolic syndrome, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objective: Non-Alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease in Western populations. While obesity and metabolic abnormalities are highly frequent in bipolar disorders (BD), no studies have been performed to estimate the prevalence of NALFD in individuals with BD. The aim of our study is to estimate the prevalence of NAFLD and to identify the potential associated risk factors in a large sample of BD individuals.Methods: Between 2009 and 2019, 1969 BD individuals from the FACE-BD cohort were included. Individuals with liver diseases, Hepatitis B or C, and current alcohol use disorders were excluded from the analyses. A blood sample was drawn from participants. Screening of NAFLD was determined using fatty liver index (FLI). Individuals with FLI> 60 were considered as having NAFLD.Results: The prevalence of NAFDL in this sample was estimated at 28.4%. NAFLD was observed in 40% of men and 21% of women. NAFLD was independently associated with older age, male gender, sleep disturbances, and current use of atypical antipsychotics or anxiolytics. As expected, the prevalence of NALFD was also higher in individuals with overweight and in those with metabolic syndrome.Conclusions: This study reinforces the view that individuals with BD are highly vulnerable to metabolic and cardiovascular diseases. The prevalence of NAFLD in individuals with BD was two times higher than the prevalence reported in the general population. The regular screening of the MetS in individuals with BD should be therefore complemented by the additional screening of NAFLD among these vulnerable individuals.
Published: 2021
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18. Electrical deep neuromodulation in psychiatry

Author: Martijn Figee and Mircea Polosan
Subjects: medicine.medical_specialty, Deep brain stimulation, business.industry, medicine.medical_treatment, Dysfunctional family, Neuromodulation (medicine), Clinical trial, Obsessive-compulsive disorders, Neuroimaging, Brain stimulation, Medicine, business, Psychiatry, Depression (differential diagnoses)
Abstract: Addressing treatment refractoriness in psychiatric diseases is an essential public health objective. The last two decades have seen an increasing interest for deep brain stimulation (DBS) of several brain targets. In this chapter, we have reviewed the main DBS clinical trials in psychiatric diseases, mainly obsessive compulsive disorders (OCD) and depression, but also emerging research in other psychiatric disorders. While its efficacy and safety are confirmed, DBS is still not considered as standard therapy in psychiatry. However, advances in neuroimaging research combined to behavioral and electrophysiological data uniquely provided by DBS studies improve knowledge on physiopathology in these brain diseases. This will help define the optimal brain targets according to specific phenotype dimensions. Revealing the mechanisms of action and effects of DBS will support that its impact goes beyond a loco-regional brain stimulation and confirms that electrical neuromodulation influences brain networks. Added to the progress in neuromodulation technology, these insights will hopefully facilitate a more widespread application of this promising treatment. Future development of a personalized multimodal assessment of underlying dysfunctional brain networks will open new circuit-specific treatment perspectives that may facilitate better patient outcomes.
Published: 2021
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19. The course of bipolar disorder as a function of the presence and sequence of onset of comorbid alcohol use disorders in outpatients attending the Fondamental Advanced Centres of Expertise

Author: Sébastien Guillaume, Marion Leboyer, Frank Bellivier, Katia M'Bailara, Georges Brousse, Isabelle Biseul, Nicolas Mazer, Emilie Olié, Philippe Courtet, Raymund Schwan, Joséphine Loftus, Valentin Flaudias, Sébastien Gard, Paul Roux, Ludovic Samalin, Ophélia Godin, Romain Icick, Iréna Cussac, Pierre-Michel Llorca, Bruno Etain, Mircea Polosan, Chantal Henry, Emmanuel Haffen, Valerie Aubin, Raoul Belzeaux, Fondation FondaMental [Créteil], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier Charles Perrens [Bordeaux], CHU Clermont-Ferrand, Hôpital Princesse Grace [Monaco], Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Centre Psychothérapique de Nancy [Laxou] (CPN), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier de Versailles André Mignot (CHV), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Hôpital Louis Mourier - AP-HP [Colombes], Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoires de neurosciences intégratives et cliniques (EA 481), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), ANR-10-COHO-10-01 Institut National de la Santé et de la Recherche Médicale, Inserm Agence Nationale de la Recherche, ANR Assistance Publique - Hôpitaux de Paris, AP-HP, This research was supported by the Foundation FondaMental, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique des Hôpitaux de Paris (AP-HP), and by the Investissements d'Avenir program managed by the Agence National de la Recherche (ANR) under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. The funding sources had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript for publication., ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Charles Perrens, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Psychothérapique de Nancy (CPN), Hôpital Lapeyronie [Montpellier] (CHU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut de Génomique Fonctionnelle (IGF), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Bipolar Disorder, Alcohol use disorder, Comorbidity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, Outpatients, medicine, Prevalence, Humans, Dual diagnosis, Bipolar disorder, Clinical trajectory, Sequence of onset, Sequence (medicine), business.industry, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Alcoholism, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Binary regression, business, 030217 neurology & neurosurgery
Abstract: 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
Published: 2020
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20. Deep brain stimulation of the subthalamic nucleus in obsessive-compulsives disorders: long-term follow-up of an open, prospective, observational cohort

Author: Thierry Bougerol, Jérôme Yelnik, Luc Mallet, Alim-Louis Benabid, Sara Fernandez Vidal, Olivier David, Stephan Chabardes, Paul Krack, Mircea Polosan, Brigitte Piallat, Eric Seigneuret, Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Bern University Hospital [Berne] (Inselspital), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor, University of Geneva [Switzerland], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], and Université de Genève = University of Geneva (UNIGE)
Subjects: Male, Obsessive-Compulsive Disorder, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Deep Brain Stimulation, Anxiety, Severity of Illness Index, Cohort Studies, ddc:616.89, 0302 clinical medicine, Quality of life, Basal ganglia, Prospective Studies, Prospective cohort study, 0303 health sciences, Anxiety/etiology, Middle Aged, 3. Good health, Psychiatry and Mental health, Subthalamic nucleus, Mania, Treatment Outcome, Cohort, Female, Cohort study, Adult, medicine.medical_specialty, Deep brain stimulation, Neurosurgery, 610 Medicine & health, Deep Brain Stimulation/adverse effects, behavioral disciplines and activities, 03 medical and health sciences, Subthalamic Nucleus, Internal medicine, Deep Brain Stimulation/methods, Severity of illness, mental disorders, medicine, Humans, 030304 developmental biology, business.industry, Mania/etiology, nervous system, Obsessive-Compulsive Disorder/therapy, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: BackgroundObsessive–compulsive disorder (OCD) is a major cause of disability in western country and responsible for severe impairment of quality of life. About 10% of patients present with severe OCD symptoms and require innovative treatment such as deep brain stimulation (DBS). Among possible targets, the non-motor subthalamic nucleus (STN) is a key node of the basal ganglia circuitry, strongly connected to limbic cortical areas known to be involved in OCD.MethodWe analysed, in a prospective, observational, monocentric, open label cohort, the effect of chronic non-motor STN-DBS in 19 patients with treatment-resistant OCD consecutively operated in a single centre. Severity of OCD was evaluated using the Yale and Brown Obsessive–Compulsive Scale (YBOCS). YBOCS scores at 6, 12 and 24 months postoperatively were compared with baseline. Responders were defined by >35% improvement of YBOCS scores. Global Assessment Functioning (GAF) scale was used to evaluate the impact of improvement.ResultsAt a 24-month follow-up, the mean YBOCS score improved by 53.4% from 33.3±3.5 to 15.8±9.1 (95% CI 11.2–20.4; pConclusionChronic DBS of the non-motor STN is an effective and relatively safe procedure to treat severe OCD resistant to conventional management.
Published: 2020
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21. Trajectories of medication adherence in patients with Bipolar Disorder along 2 years-follow-up

Author: Cyrille Perchec, Groupe Face-Bd, Philippe Courtet, Jean-Michel Azorin, Katia M'Bailara, Bruno Aouizerate, N. Corréard, Frank Bellivier, Julia-Lou Consoloni, Sébastien Gard, Marion Leboyer, Bruno Etain, Pierre-Michel Llorca, Ludovic Samalin, Paul Roux, Caroline Dubertret, Raymund Schwan, Raoul Belzeaux, Emmanuel Haffen, Valerie Aubin, Mircea Polosan, Emilie Olié, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), ANR-10-COHO-10-01, ANR-11-IDEX-0004-02, This work was supported (in part) by the Fondation FondaMental, Cr?teil, France and by the Investissements d'Avenir programs managed by the ANR, France [grant numbers ANR-11-IDEX-0004-02, ANR-10-COHO-10-01]., This work was supported (in part) by the Fondation FondaMental, Créteil, France and by the Investissements d'Avenir programs managed by the ANR, France [grant numbers ANR-11-IDEX-0004-02 , ANR-10-COHO-10-01 ]., Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire de psychologie:Santé et qualité de vie, Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier Princesse Grace, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), and ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011)
Subjects: medicine.medical_specialty, Bipolar Disorder, Medication adherence, Medication Adherence, 03 medical and health sciences, 0302 clinical medicine, Rating scale, Internal medicine, medicine, Humans, In patient, Bipolar disorder, Prospective Studies, Depression (differential diagnoses), business.industry, Depression, Bipolar Disorders, medicine.disease, Mental illness, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Eating disorders, Mood, Cross-Sectional Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: 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
Published: 2020
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22. Trajectories of functioning in bipolar disorders: A longitudinal study in the FondaMental Advanced Centers of Expertise in Bipolar Disorders cohort

Author: Ophelia Godin, Marion Leboyer, Yassin Mazroui, Bruno Aouizerate, Jean-Michel Azorin, Belzeaux Raoul, Frank Bellivier, Mircea Polosan, Philippe Courtet, Caroline Dubertret, Chantal Henry, Jean-Pierre Kahn, Josephine Loftus, Emilie Olié, Christine Passerieux, Dominique Costagliola, Bruno Etain, E. Haffen, P.M. Llorca, V. Barteau, S. Bensalem, M. Laaidi, H. Laouamri, K. Souryis, S. Hotier, A. Pelletier, N. Drancourt, J.P. Sanchez, E. Saliou, C. Hebbache, J. Petrucci, L. Willaume, E. Bourdin, M. Carminati, B. Etain, E. Marlinge, J. Meheust, B. Antoniol, A. Desage, S. Gard, A. Jutant, K. Mbailara, I. Minois, L. Zanouy, C. Abettan, L. Bardin, A. Cazals, B. Deffinis, D. Ducasse, M. Gachet, A. Henrion, E. Martinerie, F. Molière, B. Noisette, G. Tarquini, R. Belzeaux, N. Correard, J. L. Consoloni, F. Groppi, L. Lescalier, J. Montant, M. Rebattu, N. Viglianese, R. Cohen, M. Milazzo, O. Wajsbrot-Elgrabli, T. Bougerol, B. Fredembach, S. Garçon, P. Grignon, A. Perrin, A.M. Galliot, I. Grévin, A.S. Cannavo, N. Kayser, P. Roux, V. Aubin, I. Cussac, M.A. Dupont, I. Medecin, N. Mazer, C. Portalier, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Probabilités, Statistiques et Modélisations (LPSM (UMR_8001)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Princesse Grace de Monaco (CHPG), Monaco, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Probabilités, Statistique et Modélisation (LPSM (UMR_8001)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Sleep Wake Disorders, 2. Zero hunger, Psychotropic Drugs, Longitudinal study, Bipolar Disorder, business.industry, General Medicine, medicine.disease, 030227 psychiatry, Cohort Studies, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Humans, Medicine, Longitudinal Studies, Bipolar disorder, business, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, Clinical psychology
Abstract: Objective: We aimed at identifying distinct trajectories of functioning and at describing their respective clinical characteristics in a cohort of individuals with bipolar disorders. Methods: We included a sample of 2351 individuals with bipolar disorders who have been followed-up to 3 years as part as the FondaMental Advanced Centers of Expertise in Bipolar Disorders cohort. Global functioning was measured using the Functioning Assessment Short Test. We used latent class mixed models to identify distinct longitudinal trajectories of functioning over 3 years. Multivariable logistic regression models were used to identify the baseline factors that were associated with the membership to each trajectory of functioning. Results: Three distinct trajectories of functioning were identified: (1) a majority of individuals (72%) had a stable trajectory of mild functional impairment, (2) 20% of individuals had a stable trajectory of severe functional impairment and (3) 8% of individuals had a trajectory of moderate functional impairment that improved over time. The membership to a trajectory of stable severe versus stable mild functional impairment was associated with unemployment, a higher number of previous hospitalizations, childhood maltreatment, a higher level of residual depressive symptoms, higher sleep disturbances, a higher body mass index and a higher number of psychotropic medications being prescribed at baseline. The model that included these seven factors led to an area under the curve of 0.85. Conclusion: This study enabled to stratify individuals with bipolar disorders according to three distinct trajectories of functioning. The results regarding the potential determinants of the trajectory of severe functional impairment needs to be replicated in independent samples. Nevertheless, these potential determinants may represent possible therapeutic targets to improve the prognosis of those patients at risk of persistent poor functioning.
Published: 2020
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23. Author response for 'Non‐Alcoholic Fatty Liver Disease in a sample of individuals with Bipolar Disorders: Results From the FACE‐BD Cohort'

Author: null Ophelia Godin, null Marion Leboyer, null Raoul Belzeaux, null Frank Bellivier, null Joséphine Loftus, null Philippe Courtet, null Caroline Dubertret, null Sebastien Gard, null Chantal Henry, null Pierre‐Michel Llorca, null Raymund Schwan, null Christine Passerieux, null Mircea Polosan, null Ludovic Samalin, null Emilie Olié, null Bruno Etain, null B. Etain, null C. Henry, null E. Olié, null M. Leboyer, null E. Haffen, null PM Llorca, null V. Barteau, null S. Bensalem, null O. Godin, null H. Laouamri, null K. Souryis, null H Mondor, null S. Hotier, null A. Pelletier, null N. Drancourt, null JP. Sanchez, null E. Saliou, null C. Hebbache, null J. Petrucci, null L. Willaume, null E. Bourdin, null F. Bellivier, null M. Carminati, null J. Maruani, null E. Marlinge, null M. Meyrel, null B. Antoniol, null A. Desage, null S. Gard, null A. Jutant, null K. Mbailara, null I. Minois, null L. Zanouy, null L. Bardin, null A. Cazals, null P. Courtet, null B. Deffinis, null D. Ducasse, null M. Gachet, null A. Henrion, null F. Molière, null B. Noisette, null G. Tarquini, null R. Belzeaux, null N. Correard, null F. Groppi, null A. Lefrere, null L. Lescalier., null E. Moreau, null J. Pastol, null M. Rebattu, null B. Roux, null N. Viglianese, null R. Cohen, null J.P. Kahn, null M. Milazzo, null O. Wajsbrot‐Elgrabli, null T. Bougerol, null B. Fredembach, null A. Suisse, null B. Halili, null A Pouchon, null M. Polosan, null A.M. Galliot, null I. Grévin, null A.S. Cannavo, null N. Kayser, null C. Passerieux, null P. Roux, null V. Aubin, null I. Cussac, null M.A Dupont, null J. Loftus, null I. Medecin, null C. Dubertret, null N. Mazer, null C. Portalier, null C. Scognamiglio, and null A. Bing
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Cohort, Fatty liver, Medicine, Non alcoholic, Sample (statistics), Disease, business, medicine.disease
Published: 2020
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24. Effectiveness, Timing and Procedural Aspects of Cognitive Behavioral Therapy after Deep Brain Stimulation for Therapy-Resistant Obsessive Compulsive Disorder

Author: Mircea Polosan, Koen Schruers, Linda Ackermans, Tim A. M. Bouwens van der Vlis, Albert F.G. Leentjens, and Meltem Görmezoğlu
Subjects: Therapy resistant, medicine.medical_specialty, Deep brain stimulation, medicine.medical_treatment, lcsh:Medicine, Review, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Obsessive compulsive, obsessive compulsive disorder, mental disorders, medicine, Combined result, METAANALYSIS, business.industry, lcsh:R, Small sample, PHARMACOTHERAPY, General Medicine, 030227 psychiatry, deep brain stimulation, cognitive behavioral therapy, Clinical trial, Cognitive behavioral therapy, Physical therapy, business, 030217 neurology & neurosurgery
Abstract: Background and aim: Deep brain stimulation (DBS) is an effective treatment for patients with severe therapy-resistant obsessive-compulsive disorder (OCD). After initiating DBS many patients still require medication and/or behavioral therapy to deal with persisting symptoms and habitual behaviors. The clinical practice of administering postoperative cognitive behavioral therapy (CBT) varies widely, and there are no clinical guidelines for this add-on therapy. The aim of this review is to assess the efficacy, timing and procedural aspects of postoperative CBT in OCD patients treated with DBS. Method: Systematic review of literature. Results: The search yielded 5 original studies, one case series and three reviews. Only two clinical trials have explicitly focused on the effectiveness of CBT added to DBS in patients with therapy-resistant OCD. These two studies both showed effectiveness of CBT. However, they had a distinctly different design, very small sample sizes and different ways of administering the therapy. Therefore, no firm conclusions can be drawn or recommendations made for administering CBT after DBS for therapy-resistant OCD. Conclusion: The effectiveness, timing and procedural aspects of CBT added to DBS in therapy-resistant OCD have hardly been studied. Preliminary evidence indicates that CBT has an added effect in OCD patients being treated with DBS. Since the overall treatment effect is the combined result of DBS, medication and CBT, future trials should be designed in such a way that they allow quantification of the effects of these add-on therapies in OCD patients treated with DBS. Only in this way information can be gathered that contributes to the development of an algorithm and clinical guidelines for concomittant therapies to optimize treatment effects in OCD patients being treated with DBS.
Published: 2020
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25. Association between anhedonia and suicidal events in patients with mood disorders: A 3-year prospective study

Author: Rémi Moirand, Sébastien Gard, Frank Bellivier, Julia Maruani, Joséphine Loftus, Pierre-Michel Llorca, Jonathan Dubois, Philippe Courtet, Chantal Henry, Etienne Allauze, Wissam El-Hage, Marion Leboyer, Jean-Baptiste Genty, Raoul Belzeaux, Olivier Doumy, Jérôme Holtzmann, Jean-Pierre Kahn, Valerie Aubin, Guillaume Vaiva, Thierry Bougerol, Djamila Bennabi, Vincent Camus, Laurent Schmitt, Michel Walter, Christophe Lançon, Thierry d'Amato, Ludovic Samalin, Bruno Etain, Raphaëlle Richieri, Mathilde Horn, Emilie Olié, Caroline Dubertret, Fanny Moliere, Florian Stephan, Emmanuel Haffen, Antoine Yrondi, Jean-Michel Azorin, Bruno Aouizerate, Isabelle Jaussent, Julien Dubreucq, Mircea Polosan, Christine Passerieux, Déborah Ducasse, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Anhedonia, media_common.quotation_subject, Suicide, Attempted, behavioral disciplines and activities, Suicide prevention, Pleasure, Suicidal Ideation, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Humans, Prospective Studies, Suicidal ideation, ComputingMilieux_MISCELLANEOUS, media_common, Suicide attempt, business.industry, Mood Disorders, Odds ratio, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Mood disorders, Marital status, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Background As almost all mental disorders are associated with increased suicidal-related behavior, anhedonia might be a trans-diagnostic dimension to target for suicide prevention. Methods For this 3-year-long prospective study, 2,839 outpatients with mood disorders were recruited. They were divided in: (a) two groups according to the occurrence or not of suicidal ideation during the follow-up, and (b) two groups according to the occurrence or not of suicide attempts during the follow-up. Anhedonia was assessed using a composite score (the French version of the 14-item Snaith-Hamilton Pleasure Scale and item 13 of the Quick Inventory of Depressive Symptomatology scale) at inclusion and at 6, 12, 24, and 36 months after inclusion. Results Patients with mood disorders and anhedonia at least at one follow-up visit had a 1.4-fold higher risk of suicidal ideation (adjusted odds ratio = 1.35; 95% confidence interval [1.07, 1.70]), even after adjustment for confounding factors of suicide risk (i.e., bipolar or unipolar disorder, sex, age, marital status, education level, antidepressant intake, personal history of suicide attempt, at least one childhood trauma, and mean of the maximum depression score during the follow-up). Conversely, association between anhedonia and suicide attempt did not remain significant after adjustment. Conclusions The significant association between anhedonia and suicide ideation in patients with mood disorders stresses the need of targeting hedonia in mood disorders, and of research focusing on the position to pleasure in life through eudaimonia.
Published: 2020
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26. Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort

Author: Nicolas Mazer, Christine Passerieux, Bruno Etain, Valerie Aubin, S Gard, Joséphine Loftus, Raoul Belzeaux, Pierre-Michel Llorca, F Poinso, Thomas Schwitzer, Ludovic Samalin, Paul Roux, Bruno Aouizerate, A. Pelletier, Ophélia Godin, Emmanuel Haffen, Emilie Olié, Caroline Dubertret, Raymund Schwan, Marion Leboyer, C. Henry, P. Courtet, Thierry Bougerol, Franck Bellivier, Mircea Polosan, L Encely, Djamila Bennabi, Fondation FondaMental [Créteil], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Psychiatrie et Neurologie personnalisées [AP-HP Hôpital Henri-Mondor] (DHU PePsy), Hôpital Henri Mondor, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Psychiatrie et de Médecine Addictologique [AP-HP, GH Saint-Louis-Lariboisière-F.Widal], AP-HP Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal, GHU Paris Psychiatrie et Neurosciences, Service de Psychiatrie [CHU Mondor], Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Princesse Grace de Monaco (CHPG), Monaco, Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Psychothérapique de Nancy-Unité D, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital psychiatrique de Nancy, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Charles Perrens, Ministère des Affaires Sociales et de la Santé ANR-10-COHO-10-01 Institut National de la Santé et de la Recherche Médicale, Inserm Assistance Publique - Hôpitaux de Paris, AP-HP, This multicenter, cross-sectional study included patients recruited into the FACE-BD (FondaMental Academic Centers of Expertise for Bipolar Disorders) cohort between June 2009 and June 2018. The FACE-BD cohort is based on a French national network of 12 BD Expert Centers (Besançon, Bordeaux, Clermont-Ferrand, Créteil, Colombes, Grenoble, Marseille, Monaco, Montpellier, Nancy, Paris and Versailles). This network was set up by the FondaMental Foundation ( www.fondation-fondamental.org ) and funded by the French Ministry of Research and the French Ministry of Health to build an infrastructure and to provide resources to follow clinical cohorts and comparative-effectiveness research on a patient population. This cohort and the clinical variables have been extensively described in a previous paper ( Henry et al., 2015 )., This work was funded by AP-HP (Assistance Publique des Hôpitaux de Paris), by the Fondation FondaMental (RTRS Santé Mentale), by the Investissements d'Avenir program, by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01, and by INSERM (Institut National de la Santé et de la Recherche Médicale). This funding source had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript for publication., Aix Marseille Université (AMU), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), and Centre hospitalier Charles Perrens [Bordeaux]
Subjects: Adult, Pediatrics, medicine.medical_specialty, Adolescent, Bipolar disorder, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Logistic regression, National cohort, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Anticonvulsant, Humans, 030212 general & internal medicine, Medical prescription, Women of childbearing age, ComputingMilieux_MISCELLANEOUS, Valproate, business.industry, Valproic Acid, Middle Aged, medicine.disease, 3. Good health, Affect, Psychiatry and Mental health, Clinical Psychology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Childbearing age, Cohort, Female, business, 030217 neurology & neurosurgery
Abstract: International audience; Background: Valproate is associated with teratogenic and neurodevelopmental effects. Several agencies have restricted the conditions of its prescription in bipolar disorders (BD). We aimed to assess the evolution of valproate prescription and the clinical profile of BD women of childbearing age receiving valproate. Methods: Based on a large national cohort, we included all BD women 16–50 years old. Sociodemographic, clinical and pharmacological data were recorded. Logistic regression analyses were used to describe variables associated with valproate prescription. Results: Of the 1018 included women 16–50 years old, 26.9% were treated with valproate with a mean daily dosage of 968 mg. The prevalence of BD women using valproate was 32.6% before May 2015 and 17.3% after May 2015 (p
Published: 2020
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27. Neuroimaging Evidence for Increased Neurite Density in Patients Taking Lithium: A Replication Study

Author: Ivy Uszynski, Pauline Favre, Mohammed K. Shakeel, Marc-Antoine d'Albis, Chantal Henry, Achille Teillac, Jean-François Mangin, Pierre-Marie Lledo, Vina M. Goghari, Mircea Polosan, Josselin Houenou, Louise Emsell, Marion Leboyer, Cyril Poupon, Charles Laidi, Samuel Sarrazin, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Building large instruments for neuroimaging: from population imaging to ultra-high magnetic fields (BAOBAB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Calgary, University of Toronto at Scarborough, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Unité Baobab (BAOBAB), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and University of Toronto [Scarborough, Canada]
Subjects: Lithium (medication), Neurite, [SDV]Life Sciences [q-bio], Neuroimaging, Lithium, 03 medical and health sciences, 0302 clinical medicine, Replication (statistics), Neurites, medicine, Humans, In patient, Applied Psychology, ComputingMilieux_MISCELLANEOUS, business.industry, General Medicine, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Diffusion Tensor Imaging, business, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience
Published: 2020
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28. Deep Brain Stimulation in Obsessive-Compulsive Disorder

Author: Albert F.G. Leentjens and Mircea Polosan
Subjects: Clinical trial, medicine.medical_specialty, Deep brain stimulation, Quality of life (healthcare), Physical medicine and rehabilitation, business.industry, Obsessive compulsive, medicine.medical_treatment, Perspective (graphical), medicine, Lack of knowledge, business, behavioral disciplines and activities
Abstract: Deep brain stimulation (DBS) is a promising treatment for patients suffering from severe obsessive-compulsive disorder (OCD) that is resistant to conventional psychotherapeutic and pharmacological therapies. Improvement of symptoms is on average about 45%, and DBS leads to both a functional improvement and an improvement of quality of life. A number of different anatomical targets are used, but current available evidence does not support the preference of any specific target over another in terms of efficacy or side effects. Lack of knowledge of differential neuroanatomical tracts underlying the various symptom dimensions of OCD and the lack of reliable biomarkers for response hamper establishing the indication for DBS, target selection, and effective programming. However, the promising results in clinical trials so far in combination with the significant progress in understanding the underlying neurocircuitry and technological developments all encourage the further development of DBS for this indication. Technological developments should be accompanied by ongoing and proactive ethical reflection. Thus, research can contribute to defining the place of DBS within treatment algorithms for OCD and will open a new perspective for OCD patients by moving the limits of refractoriness further away.
Published: 2020
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29. Glycogen synthase kinase-3β genetic polymorphisms and insomnia in depressed patients: A prospective study

Author: Laurent Becquemont, Séverine Trabado, Emmanuelle Corruble, Bruno Fève, Emmanuel Haffen, Emanuel Loeb, Céline Verstuyft, Florian Ferreri, Mircea Polosan, Jean-François Costemale-Lacoste, Romain Colle, Séverine Martin, and Khalil El Asmar
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Genotyping Techniques, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Sleep Initiation and Maintenance Disorders, Internal medicine, mental disorders, medicine, Insomnia, Humans, Prospective Studies, Prospective cohort study, Major depressive episode, Alleles, Depression (differential diagnoses), Aged, Depressive Disorder, Glycogen Synthase Kinase 3 beta, business.industry, Middle Aged, medicine.disease, Antidepressive Agents, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Mood, Mood disorders, Antidepressant, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: 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.
Published: 2018
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30. An exoskeleton controlled by an epidural wireless brain–machine interface in a tetraplegic patient: a proof-of-concept demonstration

Author: Lilia Langar, Napoleon Torres-Martinez, Fabien Sauter-Starace, Alim-Louis Benabid, Serpil Karakas, Vincent Auboiroux, Thomas Costecalde, Stephan Chabardes, Mircea Polosan, Cécile Moro, Alexandre Moly, Andrey Eliseyev, Corinne Mestais, M. Foerster, Boris Morinière, Guillaume Charvet, Alexandre Verney, Marie-Caroline Schaeffer, David Ratel, Stephane Pezzani, Tetiana Aksenova, Neil Abroug, Aurélien Lambert, Manuela Oddoux, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Grenoble, Département Intelligence Ambiante et Systèmes Interactifs (DIASI), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, This study was funded by CEA (recurrent funding), the French Ministry of Health (Grant PHRC15150124), Fondation Motrice, Fondation Nanosciences, Institut Carnot, Fonds deDotation Clinatec., Fondation Philanthropique Edmond J Safra is a major founding institution of the Clinatec Edmond J Safra Biomedical Research Center., CEA- Saclay (CEA), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: 0303 health sciences, medicine.medical_specialty, medicine.diagnostic_test, Neuroprosthetics, business.industry, [SDV]Life Sciences [q-bio], Magnetoencephalography, Electroencephalography, medicine.disease, 3. Good health, Exoskeleton, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Exoskeleton Device, Neurology (clinical), business, Spinal cord injury, Tetraplegia, 030217 neurology & neurosurgery, 030304 developmental biology, Brain–computer interface
Abstract: Summary Background Approximately 20% of traumatic cervical spinal cord injuries result in tetraplegia. Neuroprosthetics are being developed to manage this condition and thus improve the lives of patients. We aimed to test the feasibility of a semi-invasive technique that uses brain signals to drive an exoskeleton. Methods We recruited two participants at Clinatec research centre, associated with Grenoble University Hospital, Grenoble, France, into our ongoing clinical trial. Inclusion criteria were age 18–45 years, stability of neurological deficits, a need for additional mobility expressed by the patient, ambulatory or hospitalised monitoring, registration in the French social security system, and signed informed consent. The exclusion criteria were previous brain surgery, anticoagulant treatments, neuropsychological sequelae, depression, substance dependence or misuse, and contraindications to magnetoencephalography (MEG), EEG, or MRI. One participant was excluded because of a technical problem with the implants. The remaining participant was a 28-year-old man, who had tetraplegia following a C4–C5 spinal cord injury. Two bilateral wireless epidural recorders, each with 64 electrodes, were implanted over the upper limb sensorimotor areas of the brain. Epidural electrocorticographic (ECoG) signals were processed online by an adaptive decoding algorithm to send commands to effectors (virtual avatar or exoskeleton). Throughout the 24 months of the study, the patient did various mental tasks to progressively increase the number of degrees of freedom. Findings Between June 12, 2017, and July 21, 2019, the patient cortically controlled a programme that simulated walking and made bimanual, multi-joint, upper-limb movements with eight degrees of freedom during various reach-and-touch tasks and wrist rotations, using a virtual avatar at home (64·0% [SD 5·1] success) or an exoskeleton in the laboratory (70·9% [11·6] success). Compared with microelectrodes, epidural ECoG is semi-invasive and has similar efficiency. The decoding models were reusable for up to approximately 7 weeks without recalibration. Interpretation These results showed long-term (24-month) activation of a four-limb neuroprosthetic exoskeleton by a complete brain–machine interface system using continuous, online epidural ECoG to decode brain activity in a tetraplegic patient. Up to eight degrees of freedom could be simultaneously controlled using a unique model, which was reusable without recalibration for up to about 7 weeks. Funding French Atomic Energy Commission, French Ministry of Health, Edmond J Safra Philanthropic Foundation, Fondation Motrice, Fondation Nanosciences, Institut Carnot, Fonds de Dotation Clinatec.
Published: 2019
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31. Anterior pallidal deep brain stimulation for Tourette's syndrome: a randomised, double-blind, controlled trial

Author: Marie-Laure Welter, Jean-Luc Houeto, Stéphane Thobois, Benoit Bataille, Marc Guenot, Yulia Worbe, Andreas Hartmann, Virginie Czernecki, Eric Bardinet, Jerome Yelnik, Sophie Tezenas du Montcel, Yves Agid, Marie Vidailhet, Philippe Cornu, Audrey Tanguy, Solène Ansquer, Nematollah Jaafari, Emmanuel Poulet, Giulia Serra, Pierre Burbaud, Emmanuel Cuny, Bruno Aouizerate, Pierre Pollak, Stephan Chabardes, Mircea Polosan, Michel Borg, Denys Fontaine, Bruno Giordana, Sylvie Raoul, Tiphaine Rouaud, Anne Sauvaget, Isabelle Jalenques, Carine Karachi, Luc Mallet, M.L. Welter, E. Cuny, P. Derkinderen, D. Fontaine, J.L. Houeto, I. Jalenques, L. Mallet, P. Pollak, S. Thobois, A. Bissery, H. Oya, E. Bardinet, J. Yelnik, A. Buot, V. Czernecki, S. Tezenas du Montcel, A. Tanguy, M. Hajji, C. Karachi, A. Hartmann, Y. Agid, Y. Worbe, D. Dormont, M. Vidailhet, P. Cornu, B. Aouizerate, P. Burbaud, F. Durif, C. Fauchon, F. Rondepierre, P. Derost, M. Aya Kombo, M. Polosan, S. Chabardès, A. Krainik, P. Krack, B. Piallat, M. Guenot, E. Poulet, H. Klinger, G. Serra, E. Broussolle, T. Rouaud, A. Sauvaget, P. Damier, S Raoul, M. Borg, B. Giordana, M.-N. Magnie-Mauro, N. Jaafari, B. Bataille, S. Ansquer, I. Benatru, A. Fradet, E. Dugast, A. Ouerdani, E. Rabois, M. Quintin, S. Palfi, Krack, Paul, Pollak, Pierre, Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de neurochirurgie fonctionnelle [Hôpital Pierre Wertheimer - HCL], CIC AP-HP (pitie-Salpetriere)/inserm, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des Maladies du Système Nerveux [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Neuro-Imagerie de Recherche (CENIR), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Ecole de Technologie Supérieure [Montréal] (ETS), Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie et physiopathologie de la signalisation cellulaire (PPSC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Perrens, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Psychiatrie, CHU Grenoble, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Pasteur [Nice] (CHU), Service de neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre Mémoire de Ressources et de Recherche [CHU Clermont-Ferrand] (CMRR), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Hôpital de La Milétrie, Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), Department of Neurosurgery, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Service de Neurologie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, UM des troubles du mouvement, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurosciences précliniques, Clinique neurologique, Hôpital Laennec, inconnu, Inconnu, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Neurosurgery, Centre de Référence National 'Syndrome Gilles de la Tourette', Pôle des Maladies du Système Nerveux, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Station Expérimentale des Procédés Pilotes en Environnement (STEPPE), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), ANTE-INSERM U836, équipe 11, Fonctions cérébrales et neuromodulation, Clinique de psychiatrie, CHU Grenoble-CHU Grenoble, Réseau d'Etude des Gliomes, REG, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Service de Neurochirurgie [CHU Pitié-Salpêtrière], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Transduction du Signal et Plasticite Dans Le Systeme Nerveux, Gaz de France Suez (GDF Suez), CHU Pitié-Salpêtrière [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Charles Perrens [Bordeaux], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Rennes (UR), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pôle des Maladies du Système Nerveux [CHU Pitié-Salpêtrière] (Pôle MSN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Laboratoire de Psychologie et NeuroCognition (LPNC), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Mémoire de Ressources et de Recherche [CHU de Clermont-Ferrand], Service de neurologie, and Hôpital Gabriel Montpied
Subjects: Adult, Male, medicine.medical_specialty, Movement disorders, Deep brain stimulation, Deep Brain Stimulation, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Stimulation, Globus Pallidus, Severity of Illness Index, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Outcome Assessment, Health Care, Severity of illness, medicine, Clinical endpoint, Humans, Treatment Failure, Young adult, Adverse effect, ComputingMilieux_MISCELLANEOUS, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, musculoskeletal, neural, and ocular physiology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Middle Aged, nervous system diseases, ddc:616.8, 030227 psychiatry, 3. Good health, Surgery, surgical procedures, operative, nervous system, Anesthesia, Female, Neurology (clinical), medicine.symptom, business, therapeutics, 030217 neurology & neurosurgery, Tourette Syndrome
Abstract: Summary Background Deep brain stimulation (DBS) has been proposed to treat patients with severe Tourette's syndrome, and open-label trials and two small double-blind trials have tested DBS of the posterior and the anterior internal globus pallidus (aGPi). We aimed to specifically assess the efficacy of aGPi DBS for severe Tourette's syndrome. Methods In this randomised, double-blind, controlled trial, we recruited patients aged 18–60 years with severe and medically refractory Tourette's syndrome from eight hospitals specialised in movement disorders in France. Enrolled patients received surgery to implant bilateral electrodes for aGPi DBS; 3 months later they were randomly assigned (1:1 ratio with a block size of eight; computer-generated pairwise randomisation according to order of enrolment) to receive either active or sham stimulation for the subsequent 3 months in a double-blind fashion. All patients then received open-label active stimulation for the subsequent 6 months. Patients and clinicians assessing outcomes were masked to treatment allocation; an unmasked clinician was responsible for stimulation parameter programming, with intensity set below the side-effect threshold. The primary endpoint was difference in Yale Global Tic Severity Scale (YGTSS) score between the beginning and end of the 3 month double-blind period, as assessed with a Mann-Whitney-Wilcoxon test in all randomly allocated patients who received active or sham stimulation during the double-blind period. We assessed safety in all patients who were enrolled and received surgery for aGPi DBS. This trial is registered with ClinicalTrials.gov, number NCT00478842. Findings Between Dec 6, 2007, and Dec 13, 2012, we enrolled 19 patients. We randomly assigned 17 (89%) patients, with 16 completing blinded assessments (seven [44%] in the active stimulation group and nine [56%] in the sham stimulation group). We noted no significant difference in YGTSS score change between the beginning and the end of the 3 month double-blind period between groups (active group median YGTSS score 68·5 [IQR 34·0 to 83·5] at the beginning and 62·5 [51·5 to 72·0] at the end, median change 1·1% [IQR −23·9 to 38·1]; sham group 73·0 [69·0 to 79·0] and 79·0 [59·0 to 81·5], median change 0·0% [–10·6 to 4·8]; p=0·39). 15 serious adverse events (three in patients who withdrew before stimulation and six each in the active and sham stimulation groups) occurred in 13 patients (three who withdrew before randomisation, four in the active group, and six in the sham group), with infections in DBS hardware in four patients (two who withdrew before randomisation, one in the sham stimulation group, and one in the active stimulation group). Other serious adverse events included one electrode misplacement (active stimulation group), one episode of depressive signs (active stimulation group), and three episodes of increased tic severity and anxiety (two in the sham stimulation group and one in the active stimulation group). Interpretation 3 months of aGPi DBS is insufficient to decrease tic severity for patients with Tourette's syndrome. Future research is needed to investigate the efficacy of aGPi DBS for patients over longer periods with optimal stimulation parameters and to identify potential predictors of the therapeutic response. Funding French Ministry of Health.
Published: 2017
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32. P.284 Neuroimaging evidence for increased neurite density in patients with bipolar disorder taking lithium: a replication study

Author: C. Henry, P.M. Lledo, J.-F. Mangin, C. Poupon, Mircea Polosan, P. Favre, M.K. Shakeel, Louise Emsell, Marc-Antoine d'Albis, Vina M. Goghari, Marion Leboyer, Charles Laidi, I. Uszynski, Samuel Sarrazin, and J. Houenou
Subjects: Pharmacology, Neurite, Lithium (medication), business.industry, medicine.disease, Psychiatry and Mental health, Neurology, Neuroimaging, Replication (statistics), Medicine, Pharmacology (medical), In patient, Neurology (clinical), Bipolar disorder, business, Neuroscience, Biological Psychiatry, medicine.drug
Published: 2020
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33. Toward a unified connectomic target for deep brain stimulation in obsessive-compulsive disorder

Author: Ningfei Li, Juan Carlos Baldermann, Astrid Kibleur, Svenja Treu, Harith Akram, Gavin J.B. Elias, Alexandre Boutet, Andres M. Lozano, Bassam Al-Fatly, Bryan Strange, Juan Barcia, Ludvic Zrinzo, Eileen Joyce, Stephan Chabardes, Veerle Visser-Vandewalle, Mircea Polosan, Jens Kuhn, Andrea A. Kühn, and Andreas Horn
Subjects: 0303 health sciences, Deep brain stimulation, Internal capsule, Ventrolateral prefrontal cortex, business.industry, medicine.medical_treatment, Stimulation, behavioral disciplines and activities, 03 medical and health sciences, Subthalamic nucleus, surgical procedures, operative, 0302 clinical medicine, medicine.anatomical_structure, nervous system, Obsessive compulsive, Basal ganglia, medicine, business, Neuroscience, 030217 neurology & neurosurgery, Anterior cingulate cortex, 030304 developmental biology
Abstract: Multiple surgical targets have been proposed for treating obsessive-compulsive disorder (OCD) with deep brain stimulation (DBS). However, different targets may modulate the same neural network responsible for clinical improvement. Here we analyzed data from four cohorts of OCD patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC), the nucleus accumbens (NAcc) or the subthalamic nucleus (STN). Fiber tracts that were predominantly connected to electrodes in good or poor DBS responders were isolated from a normative structural connectome and assigned a predictive value. Strikingly, the same fiber bundle was related to treatment response when independently analyzing two large training cohorts that targeted either ALIC or STN. This discriminative tract is a subsection of the ALIC and connects frontal regions (such as the dorsal anterior cingulate, dACC, and ventral prefrontal, vlPFC, cortices to the STN). When informing the tract solely based on one cohort (e.g. ALIC), clinical improvements in the other (e.g. STN) could be significantly predicted, and vice versa. Finally, clinical improvements of eight patients from a third center with electrodes in the NAcc and six patients from a fourth center in which electrodes had been implanted in both STN and ALIC were significantly predicted based on this novel tract-based DBS target. Results suggest a functional role of a limbic hyperdirect pathway that projects from dACC and vlPFC to anteriomedial STN. Obsessive-compulsive symptoms seem to be tractable by modulating the specific bundle isolated here. Our results show that connectivity-derived improvement models can inform clinical improvement across DBS targets, surgeons and centers. The identified tract is now three-dimensionally defined in stereotactic standard space and will be made openly available.
Published: 2019
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34. Higher in vivo Cortical Intracellular Volume Fraction Associated with Lithium Therapy in Bipolar Disorder: A Multicenter NODDI Study

Author: Chantal Henry, Jean-François Mangin, Achille Teillac, Cyril Poupon, Pauline Favre, Marion Leboyer, Samuel Sarrazin, Marc-Antoine d'Albis, Charles Laidi, Mircea Polosan, Josselin Houenou, Pierre-Marie Lledo, Psychiatrie et Neurologie personnalisées [AP-HP Hôpital Henri-Mondor] (DHU PePsy), Hôpital Henri Mondor, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fonctions cérébrales et neuromodulation, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Fondation FondaMental [Créteil], Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Dupuis, Christine
Subjects: medicine.medical_specialty, Neurite, Lithium (medication), Bipolar disorder, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Neurite density, Grey matter, 03 medical and health sciences, 0302 clinical medicine, In vivo, Internal medicine, medicine, Grey matter increase, 030212 general & internal medicine, Prefrontal cortex, Applied Psychology, business.industry, Compartment (ship), Therapeutic effect, General Medicine, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, medicine.anatomical_structure, Endocrinology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Lithium therapy, business, medicine.drug
Abstract: Background: MRI studies in patients with bipolar disorder have suggested that lithium is associated with grey matter increases that may underlie its therapeutic effects. However, the relationship between grey matter volume and cellular microstructural changes is not straightforward, as modifications of different cellular compartments of grey matter may be involved. Objectives: Our aim was to test the hypothesis that dendritic density is higher in patients undergoing lithium therapy than in patients without lithium, using advanced modelling of water diffusion investigated with MRI. Method: We included 41 patients and 40 controls matched for age and gender from two sites. All subjects underwent 3T MRI with 3 shells of diffusion. We used neurite orientation dispersion and density imaging to compare the grey matter neurite density between patients undergoing lithium therapy or not and control subjects. Results: We found a significant group effect in the left prefrontal region (p = 0.001, Bonferroni corrected): patients without lithium had a lower frontal neurite density than controls (p = 0.009), while those on lithium had a higher mean neurite density than those without (p < 0.001). Patients on lithium were not different from controls (p = 0.08). Conclusions: This is the first study to report in vivo evidence of preserved neurite density of the prefrontal cortex in humans associated with lithium intake. Changes of intracellular volume fraction are thought to reflect changes of grey matter microstructural organization. This reinforces the hypothesis of lithium having a positive effect on the neuronal compartment in humans.
Published: 2019
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35. Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals

Author: Jess E. Sussmann, Unn K. Haukvik, Michèle Wessa, Pedro G.P. Rosa, Philip B. Mitchell, Trine Vik Lagerberg, Henk Temmingh, Christoph Abé, Tomas Hajek, Edith Pomarol-Clotet, Sonya Foley, Chantal Henry, Neda Jahanshad, Martin Alda, Franz Hozer, Harald Kugel, Mircea Polosan, Jacques Stout, Erick J. Canales-Rodríguez, Pauline Favre, Peter R. Schofield, Josselin Houenou, Michael Deppe, Gloria Roberts, Heather C. Whalley, Tiffany M. Chaim-Avancini, Norma Verdolini, Clara Alloza, Ole A. Andreassen, Marcus V. Zanetti, Salvador Sarró, Mauricio H. Serpa, Melissa Pauling, Jonathan Repple, R. Salvador, Geraldo F. Busatto, Annerine Roos, Christopher R.K. Ching, Dominik Grotegerd, Marion Leboyer, Udo Dannlowski, Lisa T. Eyler, Xavier Caseras, Francesco Benedetti, Kang Sim, Silvia Alonso-Lana, Samuel Sarrazin, Julia Linke, Bernhard T. Baune, Jean-François Mangin, Andrew M. McIntosh, Mar Fatjó-Vilas, Edouard Duchesnay, Eduard Vieta, Dan J. Stein, Stephen M. Lawrie, Paul M. Thompson, Fleur M. Howells, Elisa M T Melloni, Favre, P., Pauling, M., Stout, J., Hozer, F., Sarrazin, S., Abe, C., Alda, M., Alloza, C., Alonso-Lana, S., Andreassen, O. A., Baune, B. T., Benedetti, F., Busatto, G. F., Canales-Rodriguez, E. J., Caseras, X., Chaim-Avancini, T. M., Ching, C. R. K., Dannlowski, U., Deppe, M., Eyler, L. T., Fatjo-Vilas, M., Foley, S. F., Grotegerd, D., Hajek, T., Haukvik, U. K., Howells, F. M., Jahanshad, N., Kugel, H., Lagerberg, T. V., Lawrie, S. M., Linke, J. O., Mcintosh, A., Melloni, E. M. T., Mitchell, P. B., Polosan, M., Pomarol-Clotet, E., Repple, J., Roberts, G., Roos, A., Rosa, P. G. P., Salvador, R., Sarro, S., Schofield, P. R., Serpa, M. H., Sim, K., Stein, D. J., Sussmann, J. E., Temmingh, H. S., Thompson, P. M., Verdolini, N., Vieta, E., Wessa, M., Whalley, H. C., Zanetti, M. V., Leboyer, M., Mangin, J. -F., Henry, C., Duchesnay, E., and Houenou, J.
Subjects: Pathology, medicine.medical_specialty, Corpus callosum, Article, White matter, 03 medical and health sciences, 0302 clinical medicine, Fractional anisotropy, Cingulum (brain), Medicine, Manic-depressive illness, Bipolar disorder, Pharmacology, Trastorn bipolar, business.industry, Diagnostic markers, Anisotropia, Translational research, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, medicine.anatomical_structure, Meta-analysis, Anisotropy, business, 030217 neurology & neurosurgery, Diffusion MRI, Tractography
Abstract: Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD);\ud however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical\ud heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with\ud BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered\ud individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean\ud fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and\ud meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD\ud compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R2 = 0.041, Pcorr < 0.001) and\ud cingulum (right: R2 = 0.041, left: R2 = 0.040, Pcorr < 0.001). Lithium medication, later onset and short disease duration were related to\ud higher FA along multiple ROIs. Results of the meta-analysis showed similar effects. We demonstrated widespread WM abnormalities\ud in BD and highlighted that altered WM connectivity within the corpus callosum and the cingulum are strongly associated with BD.\ud These brain abnormalities could represent a biomarker for use in the diagnosis of BD. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
Published: 2019
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36. Clinical characteristics of bipolar disorders with postpartum depressive onset

Author: Sarah Tebeka, Ophelia Godin, Nicolas Mazer, Frank Bellivier, Philippe Courtet, Bruno Etain, Sébastien Gard, Marion Leboyer, Pierre-Michel Llorca, Joséphine Loftus, Emilie Olié, Christine Passerieux, Mircea Polosan, Raymund Schwan, Raoul Belzeaux, Caroline Dubertret, B. Etain, C. Henry, E. Olié, M. Leboyer, E. Haffen, P.M. Llorca, V. Barteau, S. Bensalem, O. Godin, H. Laouamri, K. Souryis, S. Hotier, A. Pelletier, N. Drancourt, J.P. Sanchez, E. Saliou, C. Hebbache, J. Petrucci, L. Willaume, E. Bourdin, F. Bellivier, M. Carminati, E. Marlinge, J. Meheust, B. Antoniol, A. Desage, S. Gard, A. Jutant, K. Mbailara, I. Minois, L. Zanouy, C. Abettan, L. Bardin, A. Cazals, P. Courtet, B. Deffinis, D. Ducasse, M. Gachet, A. Henrion, E. Martinerie, F. Molière, B. Noisette, G. Tarquini, J.M. Azorin, R. Belzeaux, N. Correard, J.L. Consoloni, F. Groppi, L. Lescalier, J. Montant, M. Rebattu, N. Viglianese, R. Cohen, J.P. Kahn, M. Milazzo, O. Wajsbrot-Elgrabli, T. Bougerol, B. Fredembach, A. Suisse, B. Halili, A. Pouchon, M. Polosan, A.M. Galliot, I. Grévin, A.S. Cannavo, N. Kayser, C. Passerieux, P. Roux, V. Aubin, I. Cussac, M.A. Dupont, J. Loftus, I. Medecin, C. Dubertret, N. Mazer, C. Portalier, C. Scognamiglio, A. Bing, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation FondaMental, Institut National de la Santé et de la Recherche Médicale, Assistance Publique - Hôpitaux de Paris, ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), and ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010)
Subjects: Adult, Postpartum depression, Pediatrics, medicine.medical_specialty, Bipolar Disorder, medicine.drug_class, Suicide, Attempted, Depression, Postpartum, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Bipolar disorder, Major depressive episode, Biological Psychiatry, Retrospective Studies, Pharmacology, Suicide attempt, business.industry, Mood stabilizer, Middle Aged, medicine.disease, Family life, 030227 psychiatry, 3. Good health, Cross-Sectional Studies, Cohort, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, France, medicine.symptom, business, Postpartum period
Abstract: Background Postpartum period is associated with an increased risk of bipolar disorder diagnosis and relapse, mainly major depressive episode. Onset during this period might be associated with specific characteristics. Aim To compare the socio-demographic and clinical characteristics of parous women presenting with bipolar disorder and an index depressive episode occurring during or outside the postpartum period. Methods Using the multicenter cohort FACE-BD (FondaMental Academic Centers of Expertise for Bipolar Disorders), we considered all women who started their BD with a major depressive episode and have at least one child. We compared two groups depending on the onset: in or outside the postpartum period. Results Among the 759 women who started BD with a major depressive episode, 93 (12.2%) had a postpartum onset, and 666 (87.8%) had not. Women who started BD in the postpartum period with a major depressive episode have a more stable family life, more children, an older age at onset, more Bipolar 2 disorder, less history of suicide attempts, less depressive episodes and more mood stabilizer treatments as compared to those who started with a major depressive episode outside the postpartum period. The multivariable logistic regression showed that women with an onset in the postpartum period had significantly more children, less lifetime depressive episodes and a lower rate of history of suicide attempts as compared to women with an onset outside the postpartum period. Discussion Our results suggest that women starting their BD with postpartum depression have a more favorable course of BD, especially less history of suicide attempt and less lifetime depressive episodes.
Published: 2021
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37. Suicide and suicide attempts after subthalamic nucleus stimulation in Parkinson disease

Author: Paul Krack, Anna Castrioto, Mircea Polosan, Alim-Louis Benabid, Amélie Bichon, Claire Ardouin, Valérie Fraix, Emmanuelle Schmitt, Maxime Wack, Stephan Chabardes, Eric Seigneuret, Eugénie Lhommée, Giulia Giannini, Elena Moro, Matthieu Francois, Pierre Pollak, Giannini G., Francois M., Lhommee E., Polosan M., Schmitt E., Fraix V., Castrioto A., Ardouin C., Bichon A., Pollak P., Benabid A.-L., Seigneuret E., Chabardes S., Wack M., Krack P., and Moro E.
Subjects: Male, Pediatrics, medicine.medical_specialty, Deep brain stimulation, medicine.medical_treatment, Deep Brain Stimulation, Follow-Up Studie, 03 medical and health sciences, 0302 clinical medicine, Psychiatric history, Postoperative Complications, Retrospective Studie, Subthalamic Nucleus, Medicine, Humans, 030212 general & internal medicine, Suicidal ideation, Retrospective Studies, business.industry, Medical record, Beck Depression Inventory, Retrospective cohort study, Parkinson Disease, Middle Aged, Suicide, Standardized mortality ratio, Subthalamic Nucleu, Cohort, Female, Postoperative Complication, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Human, Follow-Up Studies
Abstract: ObjectiveTo determine the postoperative attempted and completed suicide rates after subthalamic nucleus deep brain stimulation (STN-DBS) in a single-center cohort and to determine factors associated with attempted and completed suicide.MethodsWe retrospectively included all patients with Parkinson disease (PD) who underwent bilateral STN-DBS surgery at the Grenoble University Hospital between 1993 and 2016. For each patient who committed or attempted suicide, 2 patients with PD with STN-DBS without any suicidal behaviors were matched for age (±1 year), sex, and year of surgery (±2 years). Clinical data were collected from medical records. Detailed preoperative and postoperative neuropsychological evaluations, including frontal and Beck Depression Inventory (BDI) scores, were gathered.ResultsA total of 534 patients with PD were included. Completed and attempted suicide percentages were 0.75% (4 of 534) and 4.11% (22 of 534), respectively. The observed suicide rate in the first postoperative year (187.20 of 100,000 per year, 1 of 534) was higher than the expected National Observatory on Suicide Risks rate adjusted for age and sex (standardized mortality ratio 8.1). This rate remained similar over the second and third postoperative years. In a comparison of the 26 patients completing/attempting suicide and the 52 controls, the first group showed more frequent history of suicidal ideation/suicide attempts and psychotic symptoms, higher percentage of family psychiatric history, higher psychiatric medication use, and higher preoperative frontal and BDI scores on neuropsychological evaluations.ConclusionsSuicide behaviors can occur after STN-DBS, especially during the first 3 years. A careful multidisciplinary assessment and long-term follow-up are recommended to recognize and treat this potentially preventable risk for mortality.
Published: 2018

38. Dissociable Effects of Subthalamic Stimulation in Obsessive Compulsive Disorder on Risky Reward and Loss Prospects

Author: Valerie Voon, Paul Krack, Olivier David, Sina Kohl, Fabien Droux, Thierry Bougerol, Stephan Chabardes, Mircea Polosan, Voon, Valerie [0000-0001-6790-1776], Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), and Université de Genève (UNIGE)
Subjects: Adult, Male, medicine.medical_specialty, Obsessive-Compulsive Disorder, deep-brain stimulation, Disease duration, Deep Brain Stimulation, risk taking, Stimulation, behavioral disciplines and activities, 050105 experimental psychology, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Physical medicine and rehabilitation, obsessive–compulsive disorder, Risk-Taking, Double-Blind Method, Reward, Obsessive compulsive, medicine, Humans, 0501 psychology and cognitive sciences, subthalamic nucleus, Cross-Over Studies, business.industry, General Neuroscience, 05 social sciences, Middle Aged, nervous system diseases, Subthalamic nucleus, surgical procedures, operative, nervous system, Subthalamic stimulation, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Female, Risk taking, business, therapeutics, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Our daily decisions involve an element of risk, a behavioral process that is potentially modifiable. Here we assess the role of the associative-limbic subthalamic nucleus (STN) in obsessive compulsive disorder (OCD) testing on and off deep-brain stimulation (DBS) on anticipatory risk taking to obtain rewards and avoid losses. We assessed 12 OCD STN DBS in a randomized double-blind within-subject cross-over design. STN DBS decreased risk taking to rewards (p = 0.02) and greater risk taking to rewards was positively correlated with OCD severity (p = 0.01) and disease duration (p = 0.01). STN DBS was also associated with impaired subjective discrimination of loss magnitude (p
Published: 2018
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39. Outcomes for bipolar patients assessed in the French expert center network: A 2-year follow-up observational study (FondaMental Advanced Centers of Expertise for Bipolar Disorder [FACE-BD])

Author: Marion Leboyer, Frank Bellivier, Chantal Henry, Ophélia Godin, Philippe Courtet, Bruno Etain, Jean-Michel Azorin, Sébastien Gard, Valerie Aubin, Paul Roux, Jean-Pierre Kahn, Dominique Costagliola, Mircea Polosan, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Pierre et Marie Curie - Paris 6 (UPMC), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pôle de psychiatrie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-CHU Marseille, Service de psychiatrie adulte, Université Bordeaux Segalen - Bordeaux 2-Hôpital Charles Perrens, Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Psychiatrie, CHU Grenoble, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Psychiatrie et Psychologie Clinique, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital Jeanne-d'Arc, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Fondation FondaMental [Créteil], Epidémiologie Clinique et Traitement de l'Infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatrie Translationnelle (Equipe 15), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Réseau de coopération scientifique en santé mentale, Université Bordeaux Segalen - Bordeaux 2-Centre hospitalier Charles Perrens [Bordeaux], École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Cannard, Christine
Subjects: Adult, Male, medicine.medical_specialty, Bipolar Disorder, [SDV]Life Sciences [q-bio], Gee, 03 medical and health sciences, Cognition, 0302 clinical medicine, Health care, Humans, Medicine, Cognitive skill, Bipolar disorder, Social Behavior, Generalized estimating equation, Biological Psychiatry, ComputingMilieux_MISCELLANEOUS, Psychiatric Status Rating Scales, business.industry, Confounding, Middle Aged, Prognosis, medicine.disease, 3. Good health, 030227 psychiatry, Hospitalization, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Outcome and Process Assessment, Health Care, Mood, Physical therapy, Female, Observational study, France, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Objective A new health care system for patients with bipolar disorders was established in France under the auspices of Fondation FondaMental, based on thorough clinical assessment of patients and on close collaborations between expert centers and referring practitioners. We report the results of outcomes after 2 years of observational follow-up of adult patients assessed within the network. Method A total of 984 patients were included in the study. We compared several parameters (e.g., mood episodes and hospitalization) 1 year before inclusion and after 2 years of observational follow-up using the patient as his or her own control. Other outcomes were compared at baseline and during follow-up. We estimated the evolution of these parameters over a period of 2 years using mixed models for continuous parameters and a generalized estimating equation (GEE) model for categorical variables, adjusting for potential confounding factors. Results Mean age was 42.7 (±12.5) years and 58.8% were women. The number of hospitalization days decreased by 55% when comparing 1 year before inclusion vs the follow-up period. In addition, patients showed a clear functional improvement associated with a reduction of residual mood symptoms, diminished psychiatric comorbidities, improvement of sleep and a better adherence to treatment. Conclusions This study demonstrates an overall improvement of patients followed for 2 years after an assessment in expert centers for bipolar disorders. This new organization based on a thorough clinical assessment and on personalized recommendations (drug treatments, psycho-social strategies and lifestyle measures) sent to health care professionals, and actively involving patients and families, improves the prognosis of BD patients.
Published: 2017
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40. The Catechol-O-methyltransferase Val(108/158)Met Genetic Polymorphism cannot be Recommended as a Biomarker for the Prediction of Venlafaxine Efficacy in Patients Treated in Psychiatric Settings

Author: Céline Verstuyft, Emmanuelle Corruble, Romain Colle, Adela Taranu, Denis J. David, Florian Ferreri, Laurent Becquemont, Khalil El Asmar, Mircea Polosan, Team Depression and Antidepressants (INSERM UMR 1178), Santé mentale et santé publique (SMSP - U1178), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de psychiatrie [Le Kremlin-Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Service of Psychiatry, Group of Hospitals of Paris Est, Service de Psychiatrie, CHU Grenoble, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Psychologie et NeuroCognition (LPNC), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Barrière et passage des médicaments, Université Paris-Sud - Paris 11 (UP11)-IFR141, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and IFR141-Université Paris-Sud - Paris 11 (UP11)
Subjects: Adult, Male, medicine.medical_specialty, Genotype, [SDV]Life Sciences [q-bio], Venlafaxine, Catechol O-Methyltransferase, Toxicology, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, mental disorders, medicine, Humans, In patient, Prospective Studies, Major depressive episode, Psychiatry, ComputingMilieux_MISCELLANEOUS, Psychiatric Status Rating Scales, Pharmacology, Depressive Disorder, Major, Polymorphism, Genetic, Catechol-O-methyl transferase, business.industry, Venlafaxine Hydrochloride, General Medicine, Middle Aged, 3. Good health, 030227 psychiatry, Treatment Outcome, Cohort, Antidepressive Agents, Second-Generation, Antidepressant, Female, medicine.symptom, business, Biomarkers, 030217 neurology & neurosurgery, medicine.drug, rs4680
Abstract: The antidepressant venlafaxine is known to increase the turnover of cerebral monoamines, which are catabolized by the catechol-O-methyltransferase (COMT). The COMT (Val(108/158)Met, rs4680) genetic polymorphism affects the cerebral COMT activity. But whether this genetic polymorphism is associated with response to venlafaxine remains unclear. We assessed the impact of the COMT Val(108/158)Met, rs4680 genetic polymorphism on the efficacy of venlafaxine in depressed patients. This study was nested in the METADAP cohort, a real-world naturalistic treatment study in psychiatric settings. A total of 206 Caucasian patients with a unipolar major depressive episode (DSM-IVTR) treated with venlafaxine and evaluated with the Hamilton Depression Rating Scale (HDRS) were studied. One hundred and eighty patients were genotyped for the COMT Val(108/158)Met, rs4680 genetic polymorphism and classified into three genotype subgroups: Val/Val, Val/Met and Met/Met. The COMT genotype was the explanatory variable, and the variables to be explained were HDRS score, HDRS score improvement over time, response rate and remission rate. Venlafaxine had a trend to higher efficacy in the Val/Val patients as compared to Met/Met carriers, as shown by the HDRS score improvement after 3 months of treatment, but this result was not significant in mixed models [Val/Val: 59.78% (±22.4); Val/Met: 51.64% (±26.3); Met/Met: 39.52% (±27.6)]. The percentage of responders and remitters after 3 months of treatment was not significantly different in the three genotype groups, although coherent trends were shown. The COMT Val(108/158)Met, rs4680 genetic polymorphism cannot be recommended as a biomarker for the prediction of venlafaxine efficacy in patients treated in psychiatric settings.
Published: 2017
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41. Sleep quality, chronotype and metabolic syndrome components in bipolar disorders during the remission period: Results from the FACE-BD cohort

Author: Jean-Pierre Kahn, Sébastien Gard, Marion Leboyer, Christine Passerieux, Ophélia Godin, Valerie Aubin, Chantal Henry, Philippe Courtet, Joséphine Loftus, Frank Bellivier, Dominique Costagliola, Mircea Polosan, Jean-Michel Azorin, Bruno Etain, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Princesse Grace [Monaco], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Grenoble, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Charles Perrens, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre hospitalier Charles Perrens [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, and Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)
Subjects: Adult, Male, Sleep Wake Disorders, medicine.medical_specialty, Pediatrics, Bipolar Disorder, Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Pittsburgh Sleep Quality Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Surveys and Questionnaires, Bipolar disorders, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Medicine, risk factors, Humans, Circadian rhythm, Psychiatry, Triglycerides, Metabolic Syndrome, Sleep quality, business.industry, Chronotype, Small sample, Middle Aged, medicine.disease, Sleep in non-human animals, 3. Good health, 030227 psychiatry, Circadian Rhythm, Cohort, chronotype, sleep disorders, Female, Metabolic syndrome, business, Sleep, 030217 neurology & neurosurgery
Abstract: International audience; Data on sleep or circadian abnormalities and metabolic disturbances in euthymic bipolar disorders are scarce and based on small sample sizes. The aim of this study was to explore the associations between sleep disturbances, chronotype and metabolic components in a large sample of euthymic patients with bipolar disorders (BD). From 2009 to 2015, 752 individuals with bipolar disorders from the FACE-BD cohort were included and assessed for sleep quality, chronotype and metabolic components. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to confirm the diagnosis of BD. Subjective sleep quality was measured with the Pittsburgh Sleep Quality Index and chronotype with the Composite Scale of Morningness. Sociodemographic and clinical characteristics, psychotropic treatment, psychiatric comorbidities and blood samples were collected. In our sample, 22.4% of individuals with BD presented with a metabolic syndrome, 53.7% had sleep disturbances, 25.4% were considered as having an evening chronotype and 12.6% as having a morning chronotype. Independently of potential confounders, euthymic patients with sleep disturbances had a higher abdominal circumference, and patients with evening chronotype had a significantly higher level of triglycerides. There was an association between evening chronotype and an increased atherogenic index of plasma (OR = 4.8, 95%CI = 1.6-14.7). Our findings contribute the scant literature on the relationship between sleep quality, chronotype and cardiometabolic components in euthymic individuals with BD and highlight the need to improve quality of sleep and patient education about healthier sleep-hygiene practices.
Published: 2017
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42. Severe insomnia is associated with hypertriglyceridemia in women with major depression treated in psychiatry settings

Author: Mircea Polosan, Florian Ferreri, Bruno Falissard, Emmanuelle Corruble, Florence Butlen-Ducuing, Jean-François Costemale-Lacoste, Séverine Trabado, Beverley Balkau, Bruno Fève, Romain Colle, Laurent Becquemont, Céline Verstuyft, Khalil El Asmar, Emmanuel Haffen, Service de psychiatrie [Le Kremlin-Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, INSERM UMRS 1178, INSERM UMR 1185, Service de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Service de psychiatrie et de psychologie médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), CHU Pitié-Salpêtrière [APHP]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Universitaire [Grenoble] ( CHU ), Laboratoire de Psychologie et NeuroCognition ( LPNC ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Laboratoire de Neurosciences Intégratives et Cliniques - UFC ( NEURO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), AP-HP - Hôpital Saint-Antoine, Université Paris-Sud 11 - Faculté de médecine ( UP11 UFR Médecine ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Insomnia, Population, Context (language use), Major depressive disorder, Risk Assessment, Severity of Illness Index, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Risk Factors, Triglyceridemia, Sleep Initiation and Maintenance Disorders, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, mental disorders, medicine, Humans, Severe insomnia, 030212 general & internal medicine, Risk factor, Psychiatry, education, Depression (differential diagnoses), Hypertriglyceridemia, Depressive Disorder, Major, education.field_of_study, business.industry, Middle Aged, medicine.disease, Cardiovascular risk, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Cardiovascular Diseases, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cohort, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: 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≥200 mg/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.
Published: 2017
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43. Could lithium prevent the bipolar disorder brain atrophy?

Author: Mircea Polosan, Colm McDonald, Frank Bellivier, Mary L. Phillips, Amelia Versace, Louise Emsell, Michèle Wessa, F. Hozer, P. Favre, J.-F. Mangin, Julia Linke, Marion Leboyer, Samuel Sarrazin, and Paolo Brambilla
Subjects: Pharmacology, Pathology, medicine.medical_specialty, Lithium (medication), business.industry, medicine.disease, Psychiatry and Mental health, Atrophy, Neurology, medicine, Pharmacology (medical), Neurology (clinical), Bipolar disorder, business, Biological Psychiatry, medicine.drug
Published: 2017
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44. GSK-3beta rs334558 is associated with severe insomnia in patients with major depressive episode, but not with remission after antidepressant treatment

Author: Emmanuel Haffen, B. Feve, Emmanuelle Corruble, Céline Verstuyft, Jean-François Costemale-Lacoste, Séverine Trabado, Florian Ferreri, Mircea Polosan, K. El Asmar, Romain Colle, and Laurent Becquemont
Subjects: Pharmacology, medicine.medical_specialty, business.industry, Psychiatry and Mental health, Neurology, Internal medicine, medicine, Insomnia, Antidepressant, Pharmacology (medical), In patient, Neurology (clinical), medicine.symptom, business, Major depressive episode, Gsk 3beta, Biological Psychiatry
Published: 2017
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45. Effect ofGelsemium5CH and 15CH on anticipatory anxiety: a phase III, single-centre, randomized, placebo-controlled study

Author: Adeline Paris, Naoual Boujedaini, Philippe Marijnen, Mircea Polosan, Jean-Luc Cracowski, Sophie Schmidlin, Enkelejda Hodaj, and Sandrine Mouret
Subjects: Pharmacology, medicine.medical_specialty, medicine.diagnostic_test, Visual analogue scale, business.industry, Placebo-controlled study, Placebo, law.invention, Test Anxiety Scale, Randomized controlled trial, law, Heart rate, medicine, Physical therapy, Anxiety, Pharmacology (medical), Color perception test, medicine.symptom, business
Abstract: Therapeutics to treat or prevent anxiety are numerous but many people choose to try non-conventional medicine such as homeopathy. This study aimed at evaluating the effectiveness of Gelsemium 5CH and 15CH on provoked anxiety in healthy volunteers, in comparison with placebo. This was a double-blind, single-centre, randomized, placebo-controlled study. Eligible healthy men or women aged from 18 to 40 years without a history of psychiatric disorders were randomly allocated to receive Gelsemium 5 or 15CH or placebo. Anxiety was proved by performance of the Stroop colour word test (SCWT). The primary end-point was anxiety assessed by the State measure of the State-Trait Anxiety Inventory (STAI-S) as the absolute value and difference with baseline, according to the treatment received. We included 180 healthy volunteers. The distribution into each treatment group was homogenous. There was no statistical difference between groups for the values of STAI-S at baseline, just before the SCWT and the difference between these times (1.8 [0.20 to 3.4], 1.0 [-0.6 to 2.6] and 1.4 [-0.3 to 3.0] for Gelsemium 15CH, 5CH and placebo respectively). Likewise, no statistical difference was observed between groups in anxiety as measured by a Visual Analogue Scale and the Competitive State Anxiety Inventory. Mean arterial pressure and heart rate significantly increased (P < 0.001) but no interaction between time prior to provoked anxiety and treatment was shown (P = 0.59 and P = 0.46, respectively). Gelsemium 5CH and 15CH do not prevent anticipatory anxiety in the conditions used in this study.
Published: 2011
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46. Les thérapeutiques non médicamenteuses en psychiatrie

Author: Mircea Polosan and David Szekely
Subjects: Gynecology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Therapeutic resistance, Psychiatry and Mental health, Electroconvulsive therapy, Arts and Humanities (miscellaneous), Therapie cognitive, medicine, Treatment resistance, business, Applied Psychology, Application methods
Abstract: Resume La resistance therapeutique aux approches psychopharmacologiques et psychotherapiques est une difficulte frequente a laquelle le clinicien est directement confronte, avec une frequence de 20 et 30 % concernant les troubles depressifs. D’autres approches therapeutiques semblent donc incontournables pour optimiser les soins : les psychotherapies structurees telles que la TCC et les TIP ont montre leur efficacite dans les troubles anxieux et depressifs, les approches psychoeducatives ameliorent l’observance dans les pathologies chroniques. Les approches biologiques non medicamenteuses telles que l’electroconvulsivotherapie restent une therapeutique de reference dans le traitement des troubles de l’humeur et gardent une indication dans les troubles schizophreniques resistants.
Published: 2010
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47. Long-term improvement in obsessions and compulsions with subthalamic stimulation

Author: Paul Krack, Stephan Chabardes, Mircea Polosan, Claire Ardouin, Alim-Louis Benabid, Thierry Bougerol, and Pierre Pollak
Subjects: 0301 basic medicine, Male, Obsessive-Compulsive Disorder, Deep brain stimulation, Internal capsule, medicine.medical_treatment, Deep Brain Stimulation, Nucleus accumbens, behavioral disciplines and activities, Behavior control, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, Subthalamic Nucleus, Medicine, Humans, business.industry, Ventral striatum, Middle Aged, nervous system diseases, ddc:616.8, Subthalamic nucleus, surgical procedures, operative, 030104 developmental biology, medicine.anatomical_structure, nervous system, Subthalamic stimulation, Neurology (clinical), business, therapeutics, Neuroscience, 030217 neurology & neurosurgery
Abstract: Obsessive-compulsive disorder (OCD) may be conceptualized as a disorder of self-control and behavioral inhibition.1 Recent studies2,3 suggested interest in deep brain stimulation (DBS) of different subcortical brain targets such as the nucleus accumbens, anterior internal capsule/ventral striatum, and subthalamic nucleus (STN) in severe, resistant OCD. STN is a critical node of the indirect and hyperdirect basal ganglia–thalamocortical circuit. STN-DBS may release its function as a brake on behavioral programs, disinhibiting habitual responses and enabling more flexible goal-directed behavior control in OCD.4,5 Little is known about long-term outcome of STN-DBS in OCD. Based on experience in Parkinson disease, STN-DBS can induce a change from apathetic to disinhibited behavior.6 This target has also a potential impact on addictions.4,6
Published: 2015

48. Commentaries on 'Subthalamic Deep Brain Stimulation in Obsessive-Compulsive Disorder: First German Experience and Future Outlook'

Author: Mircea Polosan, Paul Krack, and Stephan Chabardes
Subjects: Obsessive-Compulsive Disorder, Deep brain stimulation, Psychotherapist, business.industry, Deep Brain Stimulation, medicine.medical_treatment, Brain, language.human_language, ddc:616.8, German, 03 medical and health sciences, 0302 clinical medicine, Obsessive compulsive, language, Humans, Medicine, Surgery, 030212 general & internal medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Published: 2016
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49. Treating major depressive episodes with antidepressants can induce or worsen metabolic syndrome: results of the METADAP cohort

Author: Mircea Polosan, Philippe Chanson, Florence Gressier, Emmanuelle Corruble, Emmanuel Haffen, B. Feve, Anne-Cécile Petit, Khalil El Asmar, Laurent Becquemont, Romain Colle, Séverine Trabado, Jean-Pierre Lépine, Florian Ferreri, Gabriel Perlemuter, Céline Verstuyft, Sylvie Brailly-Tabard, Bruno Falissard, and Céline Bourrier
Subjects: medicine.medical_specialty, medicine.drug_class, business.industry, Tricyclic antidepressant, medicine.disease, Comorbidity, Psychiatry and Mental health, medicine, Antidepressant, Major depressive disorder, Pshychiatric Mental Health, medicine.symptom, Letters to the Editor, business, Prospective cohort study, Psychiatry, Major depressive episode, Depression (differential diagnoses), Serotonin–norepinephrine reuptake inhibitor
Abstract: Recent data (1–4) show a high comorbidity between major depressive disorder and metabolic syndrome (MetS) (5), a cluster of risk factors for cardiovascular diseases and type 2 diabetes including high waist circumference, high blood pressure, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, and high fasting plasma glucose. In a context of increasing prescription of antidepressant medication (6) and evidence of weight gain induced by antidepressants (7), the impact of antidepressant treatment on MetS has to be clarified. Indeed, there has been no prospective study of reasonable sample size and duration addressing the incidence of MetS in patients with major depressive episode treated with antidepressants. This question was addressed in the METADAP, a 6-month prospective, multicentric, real-world treatment observational cohort study of 624 patients with a diagnosis of major depressive disorder and a current major depressive episode. Data were collected from November 2009 to March 2013 in six university psychiatry departments in France. Consecutive in- or out-patients, aged 18 to 65 years, with a current major depressive episode in a context of major depressive disorder (with a minimum score of 18 at the Hamilton Depression Rating Scale-17, HDRS-17) were assessed for MetS at the start of the index antidepressant treatment (M0), and one (M1), three (M3) and six (M6) months later. All of them provided their written informed consent. Patients with psychotic symptoms, bipolar disorders, psychotic disorders, eating disorders, current substance abuse or dependence, pregnancy, organic brain syndromes or severe unstable medical conditions were not included. Patients receiving antipsychotics or mood stabilizers before inclusion and/or for 4 months or more during the last year were also excluded. Antipsychotics, mood stabilizers and stimulants were not permitted during the study, because of their metabolic effects. Benzodiazepines at the minimum effective dose and for the minimum time period and psychotherapies were allowed. The index antidepressant treatment had to be a monotherapy. The drug and its dose were left to the treating psychiatrist, using “real world” treatment options. MetS was diagnosed according to the International Diabetes Federation definition (8). Participants had to have fasted and abstained from strenuous physical activity for 8 hours before examination. Triglycerides, HDL cholesterol and fasting plasma glucose levels were assessed using routine standardized laboratory methods. Thereafter, an assistant investigator blind to the major depression assessment measured waist circumference and blood pressure. Mixed-effects multivariate models were used, because they are a well-accepted method for analyzing longitudinal clinical data in which missing or mistimed observations are present (9). All regression models included main effects for time since initiation of current antidepressant treatment, age, gender, HDRS-17 score at baseline, lifetime duration of prior major depressive disorder, lifetime duration of prior antidepressant medication, antidepressant-free period before inclusion, and current antidepressant classes. Of 689 pre-included patients, 643 were included, of whom 19 had major deviations to the protocol. Thus, 624 patients were analyzed. Six had missing data for MetS at baseline. Patients’ mean age was 45.6±13.2 years; 68.7% were women, 87.5% were inpatients at baseline. Their mean HDRS-17 score at baseline was 24.7±5.0. Their mean number of previous major depressive episodes was 1.9±2.1. The average lifetime duration of major depressive disorder before inclusion was 11.5±12.2 years. The lifetime duration of antidepressant drug treatment before inclusion was 2.3±4.1 years. Upon inclusion, 22.7% of patients were antidepressant naive. The administered antidepressant was a selective serotonin reuptake inhibitor (SSRI) in 38.9% of cases, a serotonin norepinephrine reuptake inhibitor (SNRI) in 38.3%, a tricyclic antidepressant (TCA) in 8.8%, and another one in 14.0%. The mean duration of follow-up was 4.9±4.6 months. The drop-out rate was 25.9% before M1, 21.8% between M1 and M3, and 14.3% later. The main reasons for drop-out were antidepressant change (28.4%), prescription of antipsychotics or mood stabilizers (29.4%), and lost to follow-up (20.4%). In patients without MetS at baseline (N=442, 70.8%), the incidence of MetS was 11.7% at M3 and 16.5% at M6. This increase was significant (mixed-effect multivariate logistic regression: OR=2.29, 95% CI: 1.69-3.10, p
Published: 2015
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50. Deep brain stimulation for obsessive-compulsive disorder: subthalamic nucleus target

Author: Alim-Louis Benabid, Mircea Polosan, Olivier David, Alexandre Krainik, Thierry Bougerol, Paul Krack, Stephan Chabardes, and Julien Bastin
Subjects: Male, Stn, medicine.medical_treatment, Obsessive-Compulsive Disorder/pathology/psychology/*therapy, Cognitive-behavior therapy, Dbs, Hfs, Neurosurgical Procedures/adverse effects/*methods, Electroencephalography, Subthalamic nucleus, Anterior-posterior commissural, Basal ganglia, Deep brain stimulation, Obsessive-compulsive disorder, Medicine, Cingulum (brain), Pd, Treatment Failure, Ac-pc, Eeg, Age of Onset, medicine.diagnostic_test, Gaf, Stimulation "dans le Trouble Obsessionnel Compulsif", Parkinson disease, surgical procedures, operative, Treatment Outcome, Female, therapeutics, Mri, Adult, medicine.medical_specialty, Thalamus, Cbt, Nonmotor subthalamic nucleus, Nucleus accumbens, Yale-Brown obsession compulsion scale, behavioral disciplines and activities, Magnetic resonance imaging, High-frequency stimulation, Animals, Humans, Psychiatry, Impulsive Behavior/psychology/surgery, Ocd, business.industry, Y-bocs, Patient Selection, Stoc, Subthalamic Nucleus/pathology/*surgery, nervous system diseases, Electroencephalogram, nervous system, Deep Brain Stimulation/adverse effects/*methods, Orbitofrontal cortex, Surgery, Neurology (clinical), business, Global assessment of functioning, Psychiatric disorders, Neuroscience, noM-STN
Abstract: Because of its reversibility and adaptability, deep brain stimulation (DBS) has recently gained interest in psychiatric disorders, such as obsessive-compulsive disorders (OCD) and depression. In OCD, DBS is now an alternative procedure to lesions of fascicles such as the anterior capsule, which links the orbitofrontal cortex, the cingulum, and the thalamus, and has been applied to new target such as the nucleus accumbens, with promising results. However, a recent interest has been developed toward the subthalamic nucleus (STN), a key structure of the basal ganglia that connects the motor, limbic, and associative systems. It is known from patients with Parkinson disease that STN-DBS can have significant effects on mood and cognition. Those transient effects are usually seen as "side effects" in Parkinson disease, but are clues to the underappreciated role that STN plays in the limbic circuitry, a role whose precise details are as yet unknown and under active investigation. We present the rationale supporting the use of nonmotor STN as a therapeutic target to treat OCD. In particular, we discuss the recent experience and preliminary results of our group after 6 months of nonmotor STN-DBS in patients with severe OCD.
Published: 2013

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