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1. Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment in schizophrenia: results from the multicenter FACE-SZ cohort

Author: Nathan Vidal, Paul Roux, Mathieu Urbach, Cristobal Belmonte, Laurent Boyer, Delphine Capdevielle, Julie Clauss-Kobayashi, Thierry D’Amato, Romane Dassing, Caroline Dubertret, Julien Dubreucq, Guillaume Fond, Roxana-Mihaela Honciuc, Sylvain Leignier, Pierre-Michel Llorca, Jasmina Mallet, David Misdrahi, Baptiste Pignon, Romain Rey, Franck Schürhoff, Arnaud Tessier, the FACE-SZ (FondaMental Academic Centers of Expertise—Schizophrenia) Group, Christine Passerieux, Eric Brunet-Gouet, B. Aouizerate, V. Barteau, S. Bensalem, F. Berna, O. Blanc, E. Bourguignon, L. Boyer, D. CapdevielleI. Chéreau, G. Chesnoy-Servanin, T. D’Amato, A. Deloge, H. Denizot, JM. Dorey, C. Dubertret, J. Dubreucq, S. Esselin, C. Faget, C. Fluttaz, G. Fond, F. Gabayet, O. Godin, E. Haffen, RM. Honciuc, M. Jarroir, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, PM Llorca, J. Mallet, E. Metairie, D. Misdrahi, C. Passerieux, J. Petrucci, P. Peri, B. Pignon, S. Pires, C. Portalier, R. Rey, C. Roman, F. Schürhoff, K. Souryis, A. Szöke, M. Urbach, F. Vaillant, A, Vehier, P. Vidailhet, E. Vilà, G. Wahiche, H. Yazbek, and A. Zinetti-Bertschy
Subjects: neuropsychological test, schizophrenia, cholinergic antagonist, psychotropic drug, polypharmacy, Therapeutics. Pharmacology, RM1-950
Abstract: AimThe anticholinergic properties of medications are associated with poorer cognitive performance in schizophrenia. Numerous scales have been developed to assess anticholinergic burden and yet, there is no consensus indicating which anticholinergic burden scale is more relevant for patients with schizophrenia. We aimed to identify valid scales for estimating the risk of iatrogenic cognitive impairment in schizophrenia.MethodsWe identified 27 scales in a literature review. The responses to neuropsychological tests of 839 individuals with schizophrenia or schizoaffective disorder in the FACE-SZ database were collected between 2010 and 2021. We estimated the association between objective global cognitive performance and the 27 scales, the number of psychotropic drugs, and chlorpromazine and lorazepam equivalents in bivariable regressions in a cross-sectional design. We then adjusted the bivariable models with covariates: the predictors significantly associated with cognitive performance in multiple linear regressions were considered to have good concurrent validity to assess cognitive performance.ResultsEight scales, the number of psychotropic drugs, and drug equivalents were significantly associated with cognitive impairment. The number of psychotropic drugs, the most convenient predictor to compute, was associated with worse executive function (Standardized β = −0.12, p = .004) and reasoning (Standardized β = −0.08, p = .037).ConclusionAnticholinergic burden, the number of psychotropic drugs, and drug equivalents were weakly associated with cognition, thus suggesting that cognitive impairment in schizophrenia and schizoaffective disorder is explained by factors other than medication. The number of psychotropic drugs was the most parsimonious method to assess the risk of iatrogenic cognitive impairment.
Published: 2024
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2. Immuno-metabolic profile of patients with psychotic disorders and metabolic syndrome. Results from the FACE-SZ cohort

Author: Marianne Foiselle, Susana Barbosa, Ophélia Godin, Ching-Lien Wu, Wahid Boukouaci, Myrtille Andre, Bruno Aouizerate, Fabrice Berna, Caroline Barau, Delphine Capdevielle, Pierre Vidailhet, Isabelle Chereau, Laetitia Davidovic, Jean-Michel Dorey, Caroline Dubertret, Julien Dubreucq, Catherine Faget, Guillaume Fond, Sylvain Leigner, Pierre-Michel Llorca, Jasmina Mallet, David Misdrahi, Emanuela Martinuzzi, Christine Passerieux, Romain Rey, Baptiste Pignon, Mathieu Urbach, Franck Schürhoff, Nicolas Glaichenhaus, Marion Leboyer, Ryad Tamouza, F. Berna, E. Haffen, M. Leboyer, P.M. Llorca, F. Schürhoff, V. Barteau, S. Bensalem, O. Godin, H. Laouamri, K. Souryis, I. Offerlin-Meyer, B. Pignon, A. Szöke, B. Aouizerate, A. Deloge, D. Misdrahi, E. Vilà, O. Blanc, I. Chéreau, H. Denizot, R.M. Honciuc, D. Lacelle, S. Pires, C. Dubertret, J. Mallet, C. Portalier, J. Dubreucq, C. Fluttaz, F. Gabayet, C. Roman, G. Chesnoy-Servanin, T. D'Amato, J.M. Dorey, R. Rey, A. Vehier, C. Lançon, C. Faget, E. Metairie, P. Peri, F. Vaillant, L. Boyer, G. Fond, P. Vidailhet, A. Zinetti-Bertschy, D. Capdevielle, H. Yazbek, S. Esselin, M. Jarroir, C. Passerieux, and M. Urbach
Subjects: Metabolic syndrome, Schizophrenia, Psychosis, Inflammation, Machine learning, Precision medicine, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Background: Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments. Method: A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors. Results: Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS. Conclusion: We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific “immuno-metabolic” profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry.
Published: 2022
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3. A multi-dimensional approach to the relationship between insight and aggressiveness in schizophrenia: Findings from the FACE-SZ cohort

Author: A. Schandrin, J. Norton, S. Raffard, B. Aouizerate, F. Berna, L. Brunel, I. Chereau-Boudet, T. D'Amato, H. Denizot, C. Dubertret, J. Dubreucq, C. Faget, G. Fond, F. Gabayet, P.M. Llorca, J. Mallet, D. Misdrahi, C. Passerieux, R. Rey, F. Schurhoff, M. Urbach, S. Bonnet, D. Capdevielle, M. Andrianarisoa, N. Bazin, O. Blanc, E. Bulzacka, G. Chesnoy-Servanin, J.M. Danion, A. Deloge, C. Delorme, J.M. Dorey, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, T. Le Gloahec, Y. Le Strat, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, L. Ramet, L. Rey, C. Roman, F. Schürhoff, A. Tessier, A.M. Tronche, F. Vaillant, A. Vehier, P. Vidailhet, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Université Montpellier 1 (UM1), Fondation FondaMental [Créteil], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut Européen des membranes (IEM), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), 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), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Psychopathologie et pharmacologie de la cognition, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier le Vinatier [Bron], Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA), Mécanique des Fluides, Energies et Environnement (EDF R&D MFEE), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Aix Marseille Université (AMU), Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), 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), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire [Grenoble] (CHU), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Colombière, Centre hospitalier Charles Perrens [Bordeaux], Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Strasbourg, Pôle de psychiatrie et d'addictologie des Hôpitaux Universitaires Henri-Mondor [Créteil], Centre hospitalier universitaire Henri-Mondor [Créteil], CHU Clermont-Ferrand, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Centre Hospitalier de Versailles André Mignot (CHV), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Montpellier (UM), FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group: M Andrianarisoa 16 , B Aouizerate 17 , N Bazin 18 , F Berna 19 , O Blanc 20 , L Brunel 16 , E Bulzacka 16 , D Capdevielle 21 , I Chereau-Boudet 20 , G Chesnoy-Servanin 22 , J M Danion 19 , T D'Amato 22 , A Deloge 23 , C Delorme 24 , H Denizot 20 , J M Dorey 22 , C Dubertret 25 , J Dubreucq 24 , C Faget 26 , C Fluttaz 24 , G Fond 27 , S Fonteneau 18 , F Gabayet 24 , E Giraud-Baro 24 , D Lacelle 20 , C Lançon 26 , H Laouamri 27 , M Leboyer 16 , T Le Gloahec 16 , Y Le Strat 25 , P M Llorca 20 , J Mallet 25 , E Metairie 26 , D Misdrahi 23 , I Offerlin-Meyer 19 , C Passerieux 18 , P Peri 26 , S Pires 20 , C Portalier 25 , L Ramet 18 , L Rey 22 , C Roman 24 , A Schandrin 28 , F Schürhoff 16 , A Tessier 23 , A M Tronche 20 , M Urbach 18 , F Vaillant 26 , A Vehier 22 , P Vidailhet 19 , E Vilà 23 , H Yazbek 21 , A Zinetti-Bertschy 19, Hôpital Charles Perrens, Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Université d'Auvergne - Clermont-Ferrand I (UdA)-CHU Clermont-Ferrand, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: Adult, Male, Adolescent, media_common.quotation_subject, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Hostility, Anger, Cohort Studies, Diagnostic Self Evaluation, Young Adult, 03 medical and health sciences, Aggressiveness, 0302 clinical medicine, medicine, Humans, Spectrum disorder, ComputingMilieux_MISCELLANEOUS, Biological Psychiatry, media_common, Aggression, Middle Aged, Awareness, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Psychotic Disorders, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Schizophrenia, Multi dimensional, Female, medicine.symptom, Insight, Psychology, 030217 neurology & neurosurgery, Diagnosis of schizophrenia, Clinical psychology
Abstract: International audience; Background: Aggressiveness is a stigma frequently associated with schizophrenia. The role of insight as a risk factor of aggressiveness remains contradictory; mainly because single measures of these states mask their complexity and heterogeneity.Methods: This study was conducted on 666 patients aged 15 and above with a DSM-IV-TR diagnosis of schizophrenia spectrum disorder, drawn from the French national network of schizophrenia expert center database. Collected data comprised socio-demographics and standardized psychiatric assessments. Aggressiveness was evaluated using the Buss-Perry Aggression Questionnaire and insight using the Scale to assess Unawareness of Mental Disorder (SUMD) and Birchwood Insight Scale (BIS).Results: Hostility was the aggressiveness dimension the most strongly associated with SUMD insight dimensions. Patients aware of their illness were nearly twice as likely to show hostility than those seriously unaware (OR = 1.95, 95% CI.: 1.08-3.5), but not when further adjusting for depression. Similarly, those aware of the consequences of their illness and of their symptoms were more hostile. Patients moderately aware of illness consequences had a higher risk of both anger and physical aggressiveness than those unaware (OR = 2.63, 95% CI.: 1.42-4.86, OR = 2.47, 95% CI.: 1.33-4.60, respectively), even when adjusting for depression for anger.Conclusion: Our study confirms that a multi-dimensional approach to insight and aggressiveness is essential to understand the types of links between these clinical states. Insight may trigger the expression of an underlying hostile tendency, maybe via depression and self-stigmatisation. This should be taken into account in therapeutic approaches to improve insight.
Published: 2019

4. The puzzle of quality of life in schizophrenia: putting the pieces together with the FACE-SZ cohort

Author: Eric Brunet-Gouet, Romain Rey, Christine Passerieux, Mathieu Urbach, Roxana-Mihaela Honciuc, Anne-Lise Bohec, Delphine Capdevielle, Sylvain Leigner, Myrtille André, Caroline Dubertret, Guillaume Fond, David Misdrahi, H. Laouamri, Bruno Aouizerate, Isabelle Chereau, Baptiste Pignon, Julien Dubreucq, Paul Roux, Julie Clauss, Fabrice Berna, Franck Schürhoff, Jasmina Mallet, Mickael Ehrminger, Christophe Lançon, 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 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, Fondation FondaMental [Créteil], Département de psychiatrie adulte, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital La Colombière, Hôpital Charles Perrens, 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), Les Hôpitaux Universitaires de Strasbourg (HUS), 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 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), Centre Hospitalier le Vinatier [Bron], 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), CHU Clermont-Ferrand, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Diderot - Paris 7 (UPD7), CHU Grenoble, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), 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)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), Centre de recherche en neurosciences de Lyon (CRNL), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre hospitalier Charles Perrens [Bordeaux], 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), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
Subjects: mediation analyses, Mediation (statistics), structural equation modeling, Structural equation modeling, Cohort Studies, 03 medical and health sciences, Cognition, 0302 clinical medicine, Quality of life, medicine, Humans, Applied Psychology, Cognitive reserve, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Mechanism (biology), medicine.disease, humanities, 030227 psychiatry, Psychiatry and Mental health, Cross-Sectional Studies, quality of life, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Schizophrenic Psychology, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: BackgroundThe determinants of quality of life (QoL) in schizophrenia are largely debated, mainly due to methodological discrepancies and divergence about the concepts concerned. As most studies have investigated bi- or tri-variate models, a multivariate model accounting for simultaneous potential mediations is necessary to have a comprehensive view of the determinants of QOL. We sought to estimate the associations between cognitive reserve, cognition, functioning, insight, depression, schizophrenic symptoms, and QoL in schizophrenia and their potential mediation relationships.MethodsWe used structural equation modeling with mediation analyses to test a model based on existing literature in a sample of 776 patients with schizophrenia from the FondaMental Foundation FACE-SZ cohort.ResultsOur model showed a good fit to the data. We found better functioning to be positively associated with a better QoL, whereas better cognition, better insight, higher levels of depression, and schizophrenic symptoms were associated with a lower QoL in our sample. Cognitive reserve is not directly linked to QoL, but indirectly in a negative manner via cognition. We confirm the negative relationship between cognition and subjective QoL which was previously evidenced by other studies; moreover, this relationship seems to be robust as it survived in our multivariate model. It was not explained by insight as some suggested, thus the mechanism at stake remains to be explained.ConclusionThe pathways to subjective QoL in schizophrenia are complex and the determinants largely influence each other. Longitudinal studies are warranted to confirm these cross-sectional findings.
Published: 2020

5. Precision psychiatry with immunological and cognitive biomarkers: a multi-domain prediction for the diagnosis of bipolar disorder or schizophrenia using machine learning

Author: Marion Leboyer, Nora Hamdani, Svetha Venkatesh, Jean Romain Richard, John Yearwood, Truyen Tran, Chandan Karmakar, Robert H. Yolken, Ryad Tamouza, Brisa Simoes Fernandes, H. Laouamri, and Michael Berk
Subjects: medicine.medical_specialty, Bipolar Disorder, Neuropsychological Tests, Molecular neuroscience, Machine learning, computer.software_genre, Article, lcsh:RC321-571, Machine Learning, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cognition, 0302 clinical medicine, medicine, Humans, Bipolar disorder, Psychiatry, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, business.industry, Diagnostic markers, medicine.disease, Inflammatory biomarkers, Peripheral blood, 030227 psychiatry, Psychiatry and Mental health, Multi domain, Immunological Factors, Schizophrenia, Artificial intelligence, Differential diagnosis, business, computer, Biomarkers, 030217 neurology & neurosurgery
Abstract: Precision psychiatry is attracting increasing attention lately as a recognized priority. One of the goals of precision psychiatry is to develop tools capable of aiding a clinically informed psychiatric diagnosis objectively. Cognitive, inflammatory and immunological factors are altered in both bipolar disorder (BD) and schizophrenia (SZ), however, most of these alterations do not respect diagnostic boundaries from a phenomenological perspective and possess great variability in different individuals with the same phenotypic diagnosis and, consequently, none so far has proven to have the ability of reliably aiding in the differential diagnosis of BD and SZ. We developed a probabilistic multi-domain data integration model consisting of immune and inflammatory biomarkers in peripheral blood and cognitive biomarkers using machine learning to predict diagnosis of BD and SZ. A total of 416 participants, being 323, 372, and 279 subjects for blood, cognition and combined biomarkers analysis, respectively. Our multi-domain model performances for the BD vs. control (sensitivity 80% and specificity 71%) and for the SZ vs. control (sensitivity 84% and specificity 81%) pairs were high in general, however, our multi-domain model had only moderate performance for the differential diagnosis of BD and SZ (sensitivity 71% and specificity 73%). In conclusion, our results show that the diagnosis of BD and of SZ, and that the differential diagnosis of BD and SZ can be predicted with possible clinical utility by a computational machine learning algorithm employing blood and cognitive biomarkers, and that their integration in a multi-domain outperforms algorithms based in only one domain. Independent studies are needed to validate these findings.
Published: 2020

6. Key findings on bipolar disorders from the longitudinal FondaMental Advanced Center of Expertise-Bipolar Disorder (FACE-BD) cohort

Author: M. Leboyer, O. Godin, P.M. Llorca, V. Aubin, F. Bellivier, R. Belzeaux, P. Courtet, D. Costagliola, C. Dubertret, K. M'Bailara, E. Haffen, C. Henry, H. Laouamri, C. Passerieux, A. Pelletier, M. Polosan, P. Roux, R. Schwan, L. Samalin, E. Olié, Bruno Etain, B. Etain, V. Barteau, S. Bensalem, K. Souryis, S. Hotier, J.P. Sanchez, E. Saliou, C. Hebbache, J. Petrucci, L. Wuillaume, E. Bourdin, M. Carminati, V. Hennion, E. Marlinge, J. Meheust, C. Zekri, A. Desage, S. Gard, I. Minois, J. Sportich, L. Zanouy, C. Abettan, L. Bardin, A. Cazals, B. Deffinis, D. Ducasse, M. Gachet, A. Henrion, E. Martinerie, F. Molière, B. Noisette, E.G. Tarquini, 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), CHU Henri Mondor, Fondation FondaMental [Créteil], CHU Clermont-Ferrand, 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 Princesse Grace, 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), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Hôpital Louis Mourier - AP-HP [Colombes], Laboratoire de psychologie:Santé et qualité de vie, Université Bordeaux Segalen - Bordeaux 2, Hôpital Charles Perrens, 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 [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), GHU Paris Psychiatrie et Neurosciences, 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, Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université de Lorraine (UL), This research was supported by the Foundation FondaMental, Institut National de la Sant ́e et de la Recherche M ́edicale (INSERM), AP-HP, and by the Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. Thisfunding source had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript forpublication., ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), 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), Département Médico-Universitaire Neurosciences [Sorbonne Université] (DMU Neurosciences), CHU Charles Foix [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)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Médico-Universitaire Épidémiologie et biostatistique, Santé publique, Pharmacie, Pharmacologie, Recherche, Information médicale, Thérapeutique et médicaments) (DMU Esprit), Laboratoires de neurosciences intégratives et cliniques (EA 481), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), IMRB - 'Biologie du système neuromusculaire' [Créteil] (U955 Inserm - UPEC), École nationale vétérinaire - Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Pôle de psychiatrie et d'addictologie des Hôpitaux Universitaires Henri-Mondor [Créteil], Centre hospitalier universitaire Henri-Mondor [Créteil], 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, FondaMental Advanced Center of Expertise for Bipolar Disorders (FACE-BD) collaborators : B.Etain, E.Olié, M.Leboyer, P.M.Llorca, V.Barteau, S.Bensalem, O.Godin, H.Laouamri, K.Souryis, S.Hotier, A.Pelletier, J.P.Sanchez, E.Saliou, C.Hebbache, J.Petrucci, L.Wuillaume, E.Bourdin, F.Bellivier, M.Carminati, V.Hennion, E.Marlinge, J.Meheust, C.Zekri, A.Desage, S.Gard, K.M'Bailara, I.Minois, J.Sportich, L.Zanouy, C.Abettan, L.Bardin, A.Cazals, P.Courtet, B.Deffinis, D.Ducasse, M.Gachet, A.Henrion, E.Martinerie, F.Molière, B.Noisette, E.G.Tarquini., CHU Henri Mondor [Créteil], Centre hospitalier Charles Perrens [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], CHU Saint-Antoine [AP-HP], 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Godin, Ophélia
Subjects: Bipolar Disorder, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Suicide, Attempted, Comorbidity, Environment, Anxiety Disorders, Longitudinal, Cohort Studies, Psychiatry and Mental health, Clinical Psychology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Bipolar disorders, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Course, ComputingMilieux_MISCELLANEOUS, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: The FACE-BD cohort is an observational cohort of individuals with bipolar disorders (BD) who benefited from a systematic evaluation with evidence-based treatment recommendations and who were followed-up every year for 3 years in France. The objectives were to describe the lifetime course of BD, associated psychiatric and somatic comorbidities, and cognition profile. This cohort aims to identify clinical/biological signatures of outcomes, trajectories of functioning and transition between clinical stages. This article summarizes 10 years of findings of the FACE-BD cohort.Method & results: We included 4422 individuals, all having a baseline assessment, among which 61.2% had at least one follow-up visit at either one, two or three years. A subsample of 1200 individuals had at least one biological sample (serum, plasma, DNA). Assessments include family history of psychiatric disorders, psychiatric diagnosis, current mood symptoms, functioning, hospitalizations, suicidal attempts, physical health, routine blood tests, treatment history, psychological dimensions, medico-economic data and a cognitive assessment. Studies from this cohort illustrate that individuals with BD display multiple coexistent psychiatric associated conditions including sleep disturbances, anxiety disorders, substance use disorders and suicide attempts as well as a high prevalence of metabolic syndrome. During follow-up, we observed a 55% reduction of the number of days of hospitalization and a significant improvement in functioning.Conclusions: The FACE-BD cohort provides a strong research infrastructure for clinical research in BD and has a unique position among international cohorts because of its comprehensive clinical assessment and sustainable funding from the French Ministry of Health.
Published: 2021

7. Clinical predictors of recurrences in bipolar disorders type 1 and 2: A FACE-BD longitudinal study

Author: B. Etain, F. Bellivier, E. Olié, B. Aouizerate, V. Aubin, R. Belzeaux, P. Courtet, C. Dubertret, R. Schwan, P. Roux, M. Polosan, M. Leboyer, O. Godin, P.M. Llorca, C. Henry, V. Barteau, S. Bensalem, H. Laouamri, K. Souryis, S. Hotier, A. Pelletier, J.P. Sanchez, E. Saliou, C. Hebbache, J. Petrucci, L. Willaume, E. Bourdin, M. Carminati, J. Maruani, 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, J.M. Azorin, N. Correard, J.L. Consoloni, F. Groppi, L. Lescalier, J. Montant, M. Rebattu, N. Viglianese, R. Cohen, G. Gross, T. Schwitzer, O. Wajsbrot-Elgrabli, T. Bougerol, B. Fredembach, A. Suisse, B. Halili, Z. Gaoua, A.S. Cannavo, A.M. Galliot, I. Grévin, N. Kayser, G. Liaskovski, C. Passerieux, I. Cussac, M.A. Dupont, J. Loftus, I. Medecin, N. Mazer, C. Portalier, C. Scognamiglio, A. Bing, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Fondation FondaMental [Créteil], Hôpital Fernand Widal, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Integrated Nutrition and Neurobiology, UMR 1286, INRA, Centre Hospitalier Princesse Grace, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Medico-surgical ICU, Assistance Publique - Hôpitaux de Paris, DMU ESPRIT, Médecine Intensive Réanimation, Hôpital Louis Mourier, 92700, Colombes, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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 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, Inserm, U1216, Grenoble, France., Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatrie et Neurologie personnalisées [AP-HP Hôpital Henri-Mondor] (DHU PePsy), Hôpital Henri Mondor, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Versailles André Mignot (CHV), ANR-10-COHO-10-01 Institut National de la Santé et de la Recherche Médicale, Inserm Ministère des Affaires Sociales et de la Santé, This research was supported by the Foundation FondaMental , Institut National de la Santé et de la Recherche Médicale (INSERM) , AP-HP , and by the Investissements d’Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. 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., This research was supported by the Foundation FondaMental, Institut National de la Sant? et de la Recherche M?dicale (INSERM), AP-HP, and by the Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. 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., The study sample consisted in patients evaluated in the French network of FondaMental Advanced Centers of Expertise in Bipolar Disorders (FACE-BD). This network is supported by the French Ministry of Health and has been developed under the aegis of the FondaMental Foundation, to provide support to general practitioners and psychiatrists in the diagnosis and management of patients with BD., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: medicine.medical_specialty, Longitudinal study, Clinical variables, Bipolar disorder, Subtype, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Daily practice, medicine, Humans, Longitudinal Studies, Age of Onset, First Recurrence, Biological Psychiatry, business.industry, medicine.disease, 030227 psychiatry, Affect, Psychiatry and Mental health, Mood, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, Prediction, 030217 neurology & neurosurgery
Abstract: International audience; Objective: To examine which characteristics predict the time to a first mood recurrence at three years in Bipolar Disorder type I (BD-I) and type II (BD-II). Methods: Individuals with BD were followed up to 3 years. Turbull's extension of the Kaplan-Meier analysis for interval-censored data was used to estimate the cumulative probability of recurrence over time. Separate models were performed according to BD subtype to determine which baseline factors were predictive of recurrences and were adjusted for age, gender and educational level. Results: We included 630 individuals with BD-I and 505 with BD-II. The first recurrence of any polarity occurred earlier in BD-II (p = 0.03). The first depressive recurrence occurred earlier in BD-II (p < 0.0001), whereas the first (hypo)manic recurrence occurred earlier in BD-I (p = 0.0003). In BD-I, the clinical variables that were associated to the time to a first mood recurrence were depressive symptoms, lifetime rapid cycling, global activation and the number of psychotropic medications at baseline. In BD-II, the time to a first recurrence was associated with a younger age at onset of BD and a higher number of lifetime mood episodes. The Areas Under the Curve for both models were moderate. Conclusion: Predictors of recurrences showed few specificities to BD-I or BD-II. The ability to predict recurrences in BD based on socio-demographic and clinical variables remained too moderate for a transfer in daily practice. This study highlights the need for further studies that would include other types of predictors, such as molecular, cognitive or neuro-imaging ones, to achieve an accurate level of prediction of recurrences in BD.
Published: 2021

8. Immune Signatures of Treatment-Resistant Schizophrenia: A FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) Study

Author: Guillaume Fond, Philippe Le Corvoisier, F Schürhoff, A Szöke, Face-Sz Groups, I Offerlin-Meyer, Ryad Tamouza, T D′Amato, I Chéreau, J Dubreucq, E Vilà, F Gabayet, Julien Dubreucq, C Fluttaz, Wahid Boukouaci, D Misdrahi, P Vidailhet, David Misdrahi, J Mallet, B Pignon, Caroline Barau, A Vehier, C Lançon, Myrtille André, Jasmina Mallet, Baptiste Pignon, H Yazbek, Julie Clauss-Kobayashi, Christine Passerieux, J M Dorey, Caroline Dubertret, Sylvain Leignier, K Souryis, P Peri, Isabelle Chereau, F Berna, O Blanc, G Chesnoy-Servanin, S Pires, D Lacelle, A Deloge, Franck Schürhoff, Hakim Laouamri, P M Llorca, O Godin, Bruno Aouizerate, C. Portalier, Pierre-Michel Llorca, R Rey, A Zinetti-Bertschy, H Denizot, Mathieu Urbach, M Jarroir, V Barteau, C Roman, B Aouizerate, C Passerieux, S Esselin, R M Honciuc, C Dubertret, Christophe Lançon, H. Laouamri, F Vaillant, Andrei Szöke, E Metairie, Marion Leboyer, Ching-lieng Lu, M Urbach, Fabrice Berna, C Faget, Romain Rey, Ophélia Godin, E Haffen, M Leboyer, D Capdevielle, Delphine Capdevielle, Thierry D′Amato, S Bensalem, and Emilie Terro
Subjects: profile, medicine.medical_specialty, AcademicSubjects/MED00800, clozapine, Positive and Negative Syndrome Scale, immuno-inflammatory, Schizophrenia (object-oriented programming), treatment-resistant, 030227 psychiatry, schizophrenia, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Immune system, signatures, medicine, Treatment resistant schizophrenia, Psychology, Psychiatry, 030217 neurology & neurosurgery, Clozapine, Regular Articles, medicine.drug
Abstract: Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.
Published: 2021

9. Childhood Trauma increases suicidal behaviour in a treatment-resistant depression population: a FACE-DR report

Author: Antoine Yrondi, Guillaume Vaiva, Michel Walter, Thierry D Amato, Frank Bellivier, Djamila Bennabi, Thierry Bougerol, Vincent Camus, Olivier Doumy, Jean-Baptiste Genty, Emmanuel Haffen, Jérôme Holtzmann, Mathilde Horn, Christophe Lançon, Marion Leboyer, Pierre-Michel Llorca, Julia Maruani, Rémi Moirand, Fanny Molière, Jean Petrucci, Raphaelle Richieri, Ludovic Samalin, Laurent Schmitt, Florian Stephan, Philippe Courtet, Wissam El-Hage, Bruno Aouizerate, B. Aouizerate, D. Bennabi, M. Leboyer, E. Haffen, P.M. Llorca, V. Barteau, S. Bensalem, H. Laouamri, Karmene Souryis, L. Mallet, L. Yon, J. Petrucci, J.B. Genty, A. Yrondi, D. Pierre, L. Schmitt, M. Sarrail, I. Ryff, E. Beuchet, G. Tio, C. Cappe, E. Clerc, M. Garnier, R.M. Honciuc, E. Allauze, O. Blanc, F. Bellivier, N. Allaili, I. Nieto, J. Meheust, Y. Sunthavy, J. Maruani, T. Bougerol, M. Polosan, P. Courvoisier, J. Holtzmann, B. Fredembach, S. Foubert-Andreani, V. Camus, W. El Hage, T. D’Amato, F. Haesebaert, C. Dubien, M. Lefebvre, A. Meznad, J. Brunelin, R. Moirand, O. Doumy, C. Lancon, R. Richieri, P. Peri, M. Faugere, C. Faget-Agius, P. Courtet, J.P. Boulenger, F. Moliere, F. Stephan, M. Walter, C. Mesmeur, G. Vaiva, M. Horn, Fondation FondaMental [Créteil], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hopital de Bohars - CHRU Brest (CHU - BREST ), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (SPURBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), 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), Centre Hospitalier le Vinatier [Bron], 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 de Paris (UP), 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]), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), 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), CHU Grenoble, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Perrens, 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), CHU Henri Mondor, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (EA7479 SPURBO), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), 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), 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 BFC)-Université de Franche-Comté (UFC), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier Charles Perrens [Bordeaux], CHU Henri Mondor [Créteil], CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Depressive disorders, MESH: Depression, MESH: Violence, Population, Poison control, Violence, Suicide prevention, Childhood trauma, MESH: Depressive Disorder, Treatment-Resistant, Suicidal Ideation, Depressive Disorder, Treatment-Resistant, 03 medical and health sciences, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Rating scale, Surveys and Questionnaires, Humans, Medicine, MESH: Surveys and Questionnaires, Risk factor, education, Suicidal ideation, Childhood neglect, Biological Psychiatry, education.field_of_study, MESH: Humans, MESH: Suicidal Ideation, Depression, business.industry, Childhood abuse, CTQ tree, 3. Good health, 030227 psychiatry, Suicide, Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Treatment-resistant depression, medicine.symptom, Columbia Suicide Severity Rating Scale, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: International audience; Objective: In addition to heredity, exposure to early-life adversity is an important predisposing risk factor of suicidal behaviour. Although the association between Childhood Trauma (CT) and suicide risk is well documented, interactions between CT and suicidal behaviour in Treatment-Resistant Depression (TRD) populations have received little coverage. This study aimed to evaluate i) association between CT and suicidal behaviour in a TRD population, and ii) the role of personality traits and impulsiveness as potential factors of mediation in these associations.Methods: Patients were recruited from a cohort of the French network of TRD expert centers. Depressive symptom severity, CT, suicidal behaviour, personality traits, and impulsiveness were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), the Childhood Trauma Questionnaire (CTQ), the Columbia Suicide Severity Rating Scale (CSSRS), the Structured Clinical Interview for DSM-IV, the Big Five Inventory, and the Barratt Impulsivness Scale (BIS) respectively.Results: Among the 256 patients with a baseline CTQ, in relation to suicide risk for the current depressive episode, we found an association with the total CTQ scores mediated by the intensity of the current episode in a model adjusted for age and sex (total effect: β = 0.171; p = 0.011, direct effect: β = 0.135; p = 0.043; indirect effect: β = 0.036; p = 0.048). Focusing on CT subtypes, we detected an association between suicide risk and physical neglect in a model adjusted for age and sex (β = 0.301; p = 0.002), without any mediation by the intensity of the current episode. There was no mediation effect from personality traits nor impulsiveness. With regards to CSSRS to assess suicidal ideation, we did not find any association with the total CTQ score and CT subtype scores.Conclusion: We report a strong association between suicidal behaviour and CT (in particular childhood physical neglect) in a TRD population.
Published: 2021

10. 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

11. 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

12. Comparison of three scales (BIS, SUMD and BCIS) for measuring insight dimensions and their evolution after one-year of follow-up: Findings from the FACE-SZ Cohort

Author: Delphine Capdevielle, Joanna Norton, Bruno Aouizerate, Fabrice Berna, Isabelle Chereau, Thierry D'Amato, Caroline Dubertret, Julien Dubreucq, Guillaume Fond, Lançon C, Jasmina Mallet, David Misdrahi, Catherine Passerieux, Romain Rey, Franck Schurhoff, Mathieu Urbach, Pierre-Michel Llorca, Stéphane Raffard, B. Aouizerate, F. Berna, O. Blanc, D. Capdevielle, I. Chereau-Boudet, N. Coulon, T. D'Amato, J.M. Dorey, C. Dubertret, G. Fond, F. Gabayet, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, P.M. Llorca, J. Mallet, E. Metairie, D. Misdrahi, C. Passerieux, B. Pignon, P. Peri, C. Portalier, R. Rey, C. Roman, F. Schürhoff, A. Szöke, M. Urbach, A. Zinetti-Bertschy, Fondation FondaMental [Créteil], 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), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Bordeaux [Bordeaux], Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Neuropsychologie Cognitive et Physiophatologie de la Schizophrénie (Inserm U1114 - UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, CHU Clermont-Ferrand, 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), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre Hospitalier de Versailles André Mignot (CHV), 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), Université Paul-Valéry - Montpellier 3 (UPVM), This work was funded by AP-HP (Assistance Publique des Hôpitaux de Paris), Fondation FondaMental (RTRS Santé Mentale), by the Investissements d'Avenir program managed 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)., 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), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Centre de recherche en neurosciences de Lyon (CRNL), and 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)
Subjects: Psychometrics, Composite score, [SDV]Life Sciences [q-bio], Clinical state, Cognitive Insight, 03 medical and health sciences, Cognitive dimensions of notations, 0302 clinical medicine, medicine, Humans, Biological Psychiatry, Psychiatric Status Rating Scales, Cognition, Awareness, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Psychotic Disorders, Clinical Insight, Schizophrenia, Cohort, Schizophrenic Psychology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Insight, Psychology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Treatment need, Clinical psychology
Abstract: International audience; The aim of our study was to compare the performance of three different instruments measuring clinical and cognitive dimensions of insight. Data on 182 outpatients with schizophrenia and one-year follow-up assessments was drawn from the FACE-SZ cohort. Awareness of clinical state (« clinical insight ») was measured using both a clinician-rated measure (the Scale to assess Unawareness of Mental Disorder (SUMD)), and a self-report measure (the Birchwood Insight Scale (BIS). Cognitive insight was measured using a self-report measure (the Beck Cognitive Insight Scale (BCIS)). For each scale, change in insight was examined at the follow-up. Correlations between SUMD and BIS subscales measuring same dimensions were significant. BIS-BCIS correlations were weak for all combinations except between BIS illness dimension and BCIS composite score. At the follow-up, BIS and SUMD awareness of treatment need improved whereas illness and symptom awareness increased only on the SUMD. Conversely, cognitive insight composite scores decreased. Despite relatively good overall agreement between the two clinical insight instruments, considerable variability for similar insight dimensions measured by different instruments was found. Agreement between cognitive and clinical insight is moderate. Our study strengthens the argument that insight is harder to operationalize than other symptoms and may explain why it is so seldom explicitly targeted in schizophrenia treatment.
Published: 2021

13. 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

14. Effects of Cumulative Herpesviridae and Toxoplasma gondii Infections on Cognitive Function in Healthy, Bipolar, and Schizophrenia Subjects

Author: Philippe Le Corvoisier, Dodji Attiba, Stéphane Jamain, Ophélia Godin, Robert H. Yolken, Nora Hamdani, Claire Daban-Huard, Jean Romain Richard, Jean Pierre Lepine, Marion Leboyer, Marine Delavest, H. Laouamri, Faith Dickerson, Josselin Houenou, Rajagopal Krishnamoorthy, and Ryad Tamouza
Subjects: 0301 basic medicine, education.field_of_study, medicine.medical_specialty, California Verbal Learning Test, Population, Wechsler Adult Intelligence Scale, medicine.disease_cause, medicine.disease, Herpesviridae, 03 medical and health sciences, Psychiatry and Mental health, 030104 developmental biology, 0302 clinical medicine, Schizophrenia, Immunology, Memory span, medicine, Bipolar disorder, Verbal memory, Psychology, education, Psychiatry, 030217 neurology & neurosurgery
Abstract: OBJECTIVE Schizophrenia and bipolar disorder are associated with cognitive impairment leading to social disruption. While previous studies have focused on the effect of individual infectious exposure, namely, Herpesviridae viruses or Toxoplasma gondii (T gondii), on cognitive functioning, the objective of the present study was to examine the effect of multiple infections on cognitive functioning in patients with schizophrenia and bipolar disorder and in healthy controls. METHODS Seropositivity to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV), and T gondii was related to cognitive status among 423 participants (recruited between 2008 and 2014; 138 patients with bipolar disorder, 105 patients with schizophrenia [DSM-IV criteria], and 180 healthy controls) for episodic verbal memory (California Verbal Learning Test), working memory (Wechsler Adult Intelligence Scale, third edition), and premorbid intelligence quotient (National Adult Reading Test). RESULTS Seropositivity to and antibody levels of HSV-1 were significantly associated with working memory, which persisted after correction (backward digit span: β = -0.10 [0.05], χ² = 33.89, P = .0001) in the overall sample. This association was particularly strong in the control group (β = -0.18 [0.08], P = .04, Z = -3.55, P = .0008; corrected P = .012). Further, cumulative exposure to HSV-1, HSV-2, and CMV viruses and T gondii parasite was also associated with lower scores on working memory as measured by backward digit span in the overall sample (Z = 2.86, P = .004; Z = 2.47, P = .01; and Z = 3.35, P = .01, respectively). CONCLUSIONS Exposures to Herpesviridae and T gondii parasite seem to impact cognitive functioning. Because infections caused by Herpesviridae and/or T gondii parasite are quite common in the (general) population, assessing and confirming the cognitive impairment among those who have cumulative exposures is useful and of interest.
Published: 2016

15. The 10-year findings from the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ): Review and recommendations for clinical practice

Author: F. Schürhoff, G. Fond, F. Berna, E. Bulzacka, O. Godin, L. Boyer, D. Misdrahi, M. Andrianarisoa, L. Brunel, N. Coulon, B. Aouizerate, D. Capdevielle, I. Chereau, T. D’Amato, C. Dubertret, J. Dubreucq, C. Faget, F. Gabayet, J. Mallet, R. Rey, C. Lancon, C. Passerieux, A. Schandrin, M. Urbach, P. Vidailhet, M. Leboyer, P.M. Llorca, N. Bazin, O. Blanc, I. Chereau-Boudet, G. Chesnoy-Servanin, J.M. Danion, A. Deloge, C. Delorme, H. Denizot, J.M. Dorey, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, M. Jarroir, D. Lacelle, C. Lançon, H. Laouamri, T. Le Gloahec, Y. Le Strat, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, L. Ramet, C. Roman, A. Tessier, A.M. Tronche, F. Vaillant, A. Vehier, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Fondation FondaMental [Créteil], Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Université de Strasbourg (UNISTRA), Institut Européen des membranes (IEM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), 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), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, CCSD, Accord Elsevier, Aix Marseille Université (AMU), Assistance Publique-Hôpitaux de Marseille (AP-HM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Clermont Université-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), Université d'Auvergne - Clermont-Ferrand I (UdA)-CHU Clermont-Ferrand, Psychopathologie et pharmacologie de la cognition, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA), Mécanique des Fluides, Energies et Environnement (EDF R&D MFEE), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), 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), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire [Grenoble] (CHU), IHU-LIRYC, CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], and CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA)
Subjects: Inflammation, Depression, [SDV]Life Sciences [q-bio], Dépression, Syndrome métabolique, Centre expert, Metabolic syndrome, 3. Good health, 030227 psychiatry, Expert centre, Treatment, [SDV] Life Sciences [q-bio], 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Cognition, Arts and Humanities (miscellaneous), [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Schizophrenia, Schizophrénie, Traitement, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Objectives The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort. Methods More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers. Results The major findings of the FACE-SZ cohort may be summarized as follows: the metabolic syndrome is twice more frequent in schizophrenia as compared to the general population and is not correctly assessed and treated; cognitive disturbances have been found in benzodiazepine consumers and in patients with chronic low-grade peripheral inflammation; major depressive disorder (MDD) is a common current comorbid condition in about 20% of the subjects at the evaluation. MDD is associated with impaired quality of life and with increased nicotine dependency in SZ daily tobacco smokers. Improving depression and negative symptoms may be the most effective strategies to improve quality of life in schizophrenia; the duration of untreated psychosis is much longer in cannabis smokers and in subjects with an age at illness onset < 19 years. Adherence to treatment is diminished in subjects who report a subjective negative feeling after treatment intake independent of objective side effects (extrapyramidal syndrome and weight gain). Akathisia has been found in 18% of the subjects and has been associated with antipsychotic polytherapy. Conclusions In the light of these results, some recommendations for clinical care may be suggested. The early detection of schizophrenia should be specifically increased in adolescents and/or cannabis smokers. All patients should be administered a comprehensive neuropsychological evaluation at the beginning of the illness and after stabilization under treatment. Improving metabolic parameters and lifestyle (diet and physical activity) should be reinforced. The benefit/risk ratio of benzodiazepine and antipsychotic polytherapy should be regularly reevaluated and withdrawn as soon as possible. If MDD remains underdiagnosed and undertreated, improving depression may strongly improve the quality of life of SZ subjects. In the end, Cognitive Remediation Therapy and anti-inflammatory strategies should be more frequently included in therapeutic strategies.; Objectifs Le présent article propose de faire un retour sur les 10 ans d’expérience du réseau national des 10 centres experts schizophrénie Français, à travers une revue des principales publications scientifiques qui en sont issues. Méthodes À ce jour, les données de plus de 700 patients ont pu être analysées. Globalement, cette population est composée de trois quarts d’hommes, est âgée en moyenne de 32 ans, la durée moyenne de maladie est d’environ 11 ans, l’âge moyen de début de maladie est de 21 ans, la durée de psychose non traitée est d’environ un an et demi. 55 % des sujets sont consommateurs de tabac au moment de l’évaluation. Enfin, un focus sera fait sur les projets de recherche multicentriques collaboratifs déployés au sein de ce réseau. Résultats Les principales données obtenues peuvent être résumées comme suit : le syndrome métabolique reste deux fois plus fréquent dans la schizophrénie qu’en population générale et n’est pas correctement pris en charge ; des troubles cognitifs spécifiques ont été identifiés chez les patients consommateurs de benzodiazépines et chez les patients présentant une inflammation périphérique. Des spécificités liées au sexe ont également été observées ; la dépression comorbide reste très fréquente, elle est associée à une diminution de la qualité de vie et à une augmentation de la dépendance nicotinique chez les fumeurs. Prendre en charge la dépression et les symptômes négatifs pourraient fortement améliorer la qualité de vie des patients ; le délai à l’instauration du traitement est plus long pour les schizophrénies se déclenchant avant 19 ans et chez les consommateurs de cannabis. L’adhésion au traitement est diminuée chez les patients rapportant un ressenti subjectif négatif du traitement, indépendamment de la prise de poids ou d’un syndrome extrapyramidal. Enfin, l’akathisie est très fréquente et fortement associée à la polythérapie antipsychotique. Conclusions Ces résultats conduisent à formuler plusieurs recommandations. Le dépistage du trouble et le traitement devraient être renforcés chez les adolescents et les consommateurs de cannabis. Tous les patients devraient bénéficier d’une évaluation neuropsychologique au début de leur trouble, après stabilisation sous traitement, puis de façon plus espacée au cours de leur suivi. La prise en charge des paramètres métaboliques, de l’alimentation et de l’activité physique devrait être renforcée. La balance bénéfice/risque de la prescription de benzodiazépines doit être réévaluée régulièrement au regard de son impact notamment sur la cognition. La monothérapie antipsychotique est recommandée autant que possible pour limiter les effets indésirables. La dépression reste sous-diagnostiquée et doit faire l’objet d’une évaluation systématique et d’un traitement spécifique. La remédiation cognitive doit également être plus largement proposée chez les patients présentant des troubles cognitifs.
Published: 2019

16. Relationship between childhood trauma and level of insight in schizophrenia: A path-analysis in the national FACE-SZ dataset

Author: Baptiste Pignon, Mohamed Lajnef, Ophélia Godin, Marie-Maud Geoffray, Romain Rey, Jasmina Mallet, Caroline Dubertret, Paul Roux, Christine Passerieux, Laurent Marulaz, Lore Brunel, Julien Dubreucq, Sylvain Leignier, Delphine Capdevielle, Myrtille André, Bruno Aouizerate, David Misdrahi, Fabrice Berna, Pierre Vidailhet, Isabelle Chereau, Pierre-Michel Llorca, Guillaume Fond, Christophe Lançon, Marion Leboyer, Franck Schürhoff, M.D. Andrianarisoa, B. Aouizerate, F. Berna, O. Blanc, L. Brunel, E. Bulzacka, D. Capdevielle, I. Chereau-Boudet, G. Chesnoy-Servanin, Jm Danion, T. D'Amato, A. Deloge, C. Delorme, H. Denizot, J.M. Dorey, C. Dubertret, J. Dubreucq, C. Faget, C. Fluttaz, G. Fond, S. Fonteneau, F. Gabayet, E. Giraud-Baro, M.C. Hardy-Bayle, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, T. Le Gloahec, Y. Le Strat, P.M. Llorca, J. Mallet, E. Metairie, D. Misdrahi, I. Offerlin-Meyer, C. Passerieux, P. Peri, S. Pires, C. Portalier, R. Rey, C. Roman, M. Sebilleau, A. Schandrin, F. Schurhoff, A. Tessier, Am Tronche, M. Urbach, F. Vaillant, A. Vehier, P. Vidailhet, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Pôle de Psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), 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), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Fondation FondaMental [Créteil], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), 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), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Centre Hospitalier le Vinatier [Bron], Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT), Mécanique des Fluides, Energies et Environnement (EDF R&D MFEE), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Pôle de psychiatrie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-CHU Marseille, Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Pôle de Psychiatrie [Hôpital Henri Mondor], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital H. Mondor - A. Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS), Université Grenoble Alpes (UGA), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Institut National des Sciences Appliquées (INSA), Assistance Publique-Hôpitaux de Marseille (AP-HM), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées, Université d'Auvergne - Clermont-Ferrand I (UdA)-CHU Clermont-Ferrand, École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris)
Subjects: Adult, Male, Adolescent, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Psychological Trauma, Neglect, Diagnostic Self Evaluation, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Adverse Childhood Experiences, Humans, Medicine, Path analysis (statistics), Psychological abuse, Biological Psychiatry, Physical neglect, ComputingMilieux_MISCELLANEOUS, media_common, business.industry, Adult Survivors of Child Abuse, CTQ tree, Awareness, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Cross-Sectional Studies, Physical abuse, Adult Survivors of Child Adverse Events, Psychotic Disorders, Sexual abuse, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Schizophrenia, Female, business, 030217 neurology & neurosurgery, Psychopathology, Clinical psychology
Abstract: Introduction This study aimed was to investigate the relationship between different types of childhood trauma and the level of insight (i.e., awareness of having a psychiatric disorder) in subjects suffering from schizophrenia, as well as the putative role of clinical mediators. Methods 294 community-dwelling subjects with stable schizophrenia were included into FACE-SZ, a multicentre cross-sectional study. All patients were assessed by specialized multidisciplinary teams. The level of insight was assessed by the Scale to assess Unawareness of Mental Disorder (SUMD), and childhood trauma by the Childhood Trauma Questionnaire (CTQ). Path analyses from the five CTQ subscales (physical abuse and neglect, emotional abuse and neglect, and sexual abuse) and the SUMD, with current symptomatology (i.e., positive, negative, global psychopathology and depression) as mediator, was performed. Results Physical neglect (β = 0.14) and abuse (β = 0.13) were significantly associated with poor insight. Negative symptoms were a clinical mediator of the relationship between physical neglect and poor insight. Moreover, positive (β = 0.21) and negative (β = 0.30) symptoms were associated with poor insight, whereas depression (β = −0.14) was associated with higher levels of insight. Discussion For the first time, this study shows a significant relationship between childhood trauma, specifically physical neglect and abuse, and poor insight. The level of insight was linked to different clinical dimensions. Among subjects with schizophrenia, these results provide support for a role of childhood trauma in poorer management outcomes, and the need to provide treatment, including psycho-education that better targets the consequences of childhood trauma.
Published: 2019

17. Medication and aggressiveness in real-world schizophrenia. Results from the FACE-SZ dataset

Author: Mathieu Urbach, Isabelle Chereau, Dubreucq, Guillaume Fond, Lore Brunel, Bruno Aouizerate, P. Vidalhet, M. Favez, David Misdrahi, Christine Passerieux, Romain Rey, A. Schandrin, L. Boyer, C. Lançon, Delphine Capdevielle, A.M. Tronche, Fabrice Berna, H. Laouamri, Antoine Pelissolo, F. Schürhoff, Y. Le Strat, Jean-Michel Dorey, F. Gabayet, Pierre-Michel Llorca, Catherine Faget, Caroline Dubertret, Fondation FondaMental [Créteil], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), 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), 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, and Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Cross-sectional study, medicine.medical_treatment, Schizoaffective disorder, Violence, Antipsychotic, 03 medical and health sciences, Aggressiveness, 0302 clinical medicine, medicine, Young adult, Psychiatry, Pharmacology, Benzodiazepine, biology, Buss perry scale, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, biology.organism_classification, 3. Good health, 030227 psychiatry, Mood, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cannabis, Psychology, 030217 neurology & neurosurgery, Clinical psychology, Cohort study
Abstract: International audience; INTRODUCTION:The primary objective of this study was to determine if second-generation antipsychotic (SGA) administration was associated with lower aggressiveness scores compared to first-generation (FGA) in schizophrenia (SZ). The secondary objective was to determine if antidepressants, mood stabilizers, and benzodiazepines administration were respectively associated with lower aggressiveness scores compared to patients who were not administered these medications.METHODS:Three hundred thirty-one patients with schizophrenia (N = 255) or schizoaffective disorder (N = 76) (mean age = 32.5 years, 75.5 % male gender) were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with the structured clinical interview for DSM-IV Axis I disorders and validated scales for psychotic symptomatology, insight, and compliance. Aggressiveness was measured by the Buss-Perry Aggression Questionnaire (BPAQ) score. Ongoing psychotropic treatment was recorded.RESULTS:Patients who received SGA had lower BPAQ scores than patients who did not (p = 0.01). More specifically, these patients had lower physical and verbal aggression scores. On the contrary, patients who received benzodiazepines had higher BPAQ scores than patients who did not (p = 0.04). No significant difference was found between BPAQ scores of patients respectively being administered mood stabilizers (including valproate), antidepressant, and the patients who were not. These results were found independently of socio-demographical variables, psychotic symptomatology, insight, compliance into treatment, daily-administered antipsychotic dose, the way of antipsychotic administration (oral vs long acting), current alcohol disorder, and daily cannabis consumption.CONCLUSION:The results of the present study are in favor of the choice of SGA in SZ patients with aggressiveness, but these results need further investigation in longitudinal studies. Given the potent side effects of benzodiazepines (especially dependency and cognitive impairment) and the results of the present study, their long-term prescription is not recommended in patients with schizophrenia and aggressive behavior.
Published: 2015

18. Risk factors for increased duration of untreated psychosis. Results from the FACE-SZ dataset

Author: G. Fond, L. Boyer, M. Andrianarisoa, O. Godin, L. Brunel, E. Bulzacka, N. Coulon, P.M. Llorca, F. Berna, B. Aouizerate, D. Capdevielle, T. D'Amato, C. Dubertret, J. Dubreucq, C. Faget, F. Gabayet, J. Mallet, D. Misdrahi, R. Rey, R. Richieri, P. Roux, C. Passerieux, A. Schandrin, A.M. Tronche, P. Vidailhet, M. Leboyer, F. Schürhoff, O. Blanc, I. Chereau-Boudet, G. Chesnoy-Servanin, J.M. Danion, A. Deloge, C. Delorme, H. Denizot, J.M. Dorey, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, M.C. Hardy-Bayle, D. Lacelle, C. Lançon, H. Laouamri, T. Le Gloahec, Y. Le Strat, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, C. Roman, M. Sebilleau, F. Schurhoff, A. Tessier, M. Urbach, F. Vaillant, A. Vehier, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, 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), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier le Vinatier [Bron], Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), ONERA - The French Aerospace Lab [Toulouse], ONERA, Departement de Psychiatrie, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), 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)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], 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), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Hospitalier d'Annecy, Centre hospitalier d'Annecy, IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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), 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 Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, Pediatrics, medicine.medical_specialty, Multivariate analysis, Delayed Diagnosis, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Untreated psychosis, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Sex Factors, Prognosis of schizophrenia, Risk Factors, medicine, Humans, Bipolar disorder, Age of Onset, Psychiatry, Antipsychotic, Biological Psychiatry, ComputingMilieux_MISCELLANEOUS, Psychiatric Status Rating Scales, biology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, medicine.disease, biology.organism_classification, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, dup, Educational Status, Female, Schizophrenic Psychology, Cannabis, France, Independent Living, Psychology, 030217 neurology & neurosurgery
Abstract: Objectives Reducing the duration of untreated psychosis (DUP) may improve the prognosis of schizophrenia. This study investigated the prevalence, and associated risk factors, of long DUP in a large, non-selected sample of community-dwelling schizophrenia patients (SZ). Method 478 community-dwelling stable SZ participants (122 women and 356 men; mean age 32.37 ± 9.86 years) were recruited between 2010 and 2016. The mean retrospective DUP was evaluated from both patient and family reports, as well as hospital/psychiatrists records. Long DUP was defined as > 2 years. Results The mean DUP was 1.5 years. 80 participants (16.7%) had a DUP > 2 years. In multivariate analyses, after adjustment for sex, education level, history of childhood trauma and history of maternal schizophrenia or bipolar disorder, long DUP was associated with a younger age of illness onset (19.3 ± 6.67 years vs. 22.0 ± 6.51 years, adjusted odd ratio aOR = 0.91, 95%CI [0.86; 0.97], p = 0.003) and cannabis use disorder (20.0% vs. 10.3%, aOR = 2.41, 95%CI [1.14–5.09], p = 0.02). Conclusion A high proportion of SZ patients still have a long DUP. The present results suggest that illness onset before age 19 years and cannabis use are associated with long DUP in schizophrenia patients. Early psychosis detection programs should prioritize the targeting of these populations.
Published: 2018

19. Psychiatric disability as mediator of the neurocognition-functioning link in schizophrenia spectrum disorders: SEM analysis using the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale

Author: Paul Roux, Mathieu Urbach, Sandrine Fonteneau, Fabrice Berna, Lore Brunel, Delphine Capdevielle, Isabelle Chereau, Julien Dubreucq, Catherine Faget-Agius, Guillaume Fond, Sylvain Leignier, Claire-Cécile Perier, Raphaëlle Richieri, Priscille Schneider, Franck Schürhoff, Anne-Marie Tronche, Hanan Yazbek, Anna Zinetti-Bertschy, Christine Passerieux, Eric Brunet-Gouet, M. Andrianarisoa, B. Aouizerate, N. Bazin, F. Berna, O. Blanc, L. Brunel, E. Bulzacka, D. Capdevielle, I. Chereau-Boudet, G. Chesnoy-Servanin, Jm Danion, T. D'Amato, A. Deloge, C. Delorme, H. Denizot, J.M. Dorey, C. Dubertret, J. Dubreucq, C. Faget, C. Fluttaz, G. Fond, S. Fonteneau, F. Gabayet, E. Giraud-Baro, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, T. Le Gloahec, Y. Le Strat, null Llorca, J. Mallet, E. Metairie, D. Misdrahi, I. Offerlin-Meyer, C. Passerieux, P. Peri, S. Pires, C. Portalier, L. Ramet, R. Rey, C. Roman, A. Schandrin, F. Schürhoff, A. Tessier, Am Tronche, M. Urbach, F. Vaillant, A. Vehier, P. Vidailhet, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Fondation FondaMental [Créteil], 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 de Versailles André Mignot (CHV), 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, 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), 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), 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), Département de psychiatrie adulte, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital La Colombière, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, 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 ), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Psychometrics, media_common.quotation_subject, Metacognition, Remediation, Cohort Studies, 03 medical and health sciences, Disability Evaluation, Young Adult, 0302 clinical medicine, Cognition, Visual memory, Neuropsychology, medicine, Humans, Effects of sleep deprivation on cognitive performance, Functioning, Psychiatry, Biological Psychiatry, media_common, Psychiatric Status Rating Scales, Disability, Middle Aged, 030227 psychiatry, Psychiatry and Mental health, Cross-Sectional Studies, Psychotic Disorders, Cognitive remediation therapy, Latent Class Analysis, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Schizophrenia, Female, Schizophrenic Psychology, Psychology, Neurocognitive, 030217 neurology & neurosurgery, Vigilance (psychology)
Abstract: International audience; The functional outcome in schizophrenia spectrum disorders is affected by multiple factors such as cognitive performance and clinical symptoms. Psychiatric disability may be another important determinant of functional outcome. The purpose of this study was to test whether schizophrenia symptoms and psychiatric disability mediated the association between cognition and functioning. Between April 2013 and July 2017, we included 108 community-dwelling adults with stable schizophrenia spectrum disorder in a multicenter study. Psychiatric disability was assessed with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale by relatives of patients. ECPDS focused on the broad array of motivational, neurocognitive, sociocognitive, and metacognitive impairments that result in activity restrictions. We used a battery of tests to assess seven cognition domains (processing speed, attention/vigilance, working, verbal and visual memory, reasoning and problem solving, and executive functioning) and cross-sectional structural equation modeling (SEM) for the mediation analyses. We estimated the one-year temporal stability of ECPDS scores in 45 participants. The model provided showed good fit and explained 43.9% of the variance in functioning. The effect of neurocognition on functioning was fully mediated by symptoms (proportion mediated: 36.5%) and psychiatric disability (proportion mediated: 31.3%). The ECPDS score had acceptable one-year temporal stability. The ECPDS scale has satisfactory psychometric properties, and shows significant convergence with neurocognition and functioning, suggesting a role for this tool in the routine evaluation of cognitive remediation needs. Our model validates psychiatric disability as a crucial step from cognitive impairment to restricted participation in life situations.
Published: 2018

20. Supplemental_Material – Supplemental material for Screening for cognitive deficits with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia scale

Author: Roux, Paul, Urbach, Mathieu, Fonteneau, Sandrine, Berna, Fabrice, Brunel, Lore, Capdevielle, Delphine, Chereau, Isabelle, Dubreucq, Julien, Faget-Agius, Catherine, Fond, Guillaume, Leignier, Sylvain, Claire-Cécile Perier, Richieri, Raphaëlle, Schneider, Priscille, Schürhoff, Franck, Tronche, Anne Marie, Yazbek, Hanan, Zinetti-Bertschy, Anna, Passerieux, Christine, Brunet-Gouet, Eric, M Andrianarisoa, B Aouizerate, N Bazin, F Berna, O Blanc, L Brunel, E Bulzacka, D Capdevielle, I Chereau-Boudet, G Chesnoy-Servanin, JM Danion, T D’Amato, A Deloge, C Delorme, H Denizot, JM Dorey, C Dubertret, J Dubreucq, C Faget, C Fluttaz, G Fond, S Fonteneau, F Gabayet, E Giraud-Baro, D Lacelle, C Lançon, H Laouamri, M Leboyer, T Le Gloahec, Y Le Strat, PM Llorca, J Mallet, E Metairie, D Misdrahi, I Offerlin-Meyer, C Passerieux, P Peri, S Pires, C Portalier, L Ramet, R Rey, C Roman, A Schandrin, F Schürhoff, A Tessier, AM Tronche, M Urbach, F Vaillant, A Vehier, P Vidailhet, E Vilà, H Yazbek, and A Zinetti-Bertschy
Subjects: FOS: Clinical medicine, 110604 Sports Medicine, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases, 110314 Orthopaedics
Abstract: Supplemental material, Supplemental_Material for Screening for cognitive deficits with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia scale by Paul Roux, Mathieu Urbach, Sandrine Fonteneau, Fabrice Berna, Lore Brunel, Delphine Capdevielle, Isabelle Chereau, Julien Dubreucq, Catherine Faget-Agius, Guillaume Fond, Sylvain Leignier, Claire-Cécile Perier, Raphaëlle Richieri, Priscille Schneider, Franck Schürhoff, Anne Marie Tronche, Hanan Yazbek, Anna Zinetti-Bertschy, the FondaMental Advanced Centers of Expertise in Schizophrenia (FACE-SCZ) Collaborators, Christine Passerieux, Eric Brunet-Gouet, M Andrianarisoa, B Aouizerate, N Bazin, F Berna, O Blanc, L Brunel, E Bulzacka, D Capdevielle, I Chereau-Boudet, G Chesnoy-Servanin, JM Danion, T D’Amato, A Deloge, C Delorme, H Denizot, JM Dorey, C Dubertret, J Dubreucq, C Faget, C Fluttaz, G Fond, S Fonteneau, F Gabayet, E Giraud-Baro, D Lacelle, C Lançon, H Laouamri, M Leboyer, T Le Gloahec, Y Le Strat, PM Llorca, J Mallet, E Metairie, D Misdrahi, I Offerlin-Meyer, C Passerieux, P Peri, S Pires, C Portalier, L Ramet, R Rey, C Roman, A Schandrin, F Schürhoff, A Tessier, AM Tronche, M Urbach, F Vaillant, A Vehier, P Vidailhet, E Vilà, H Yazbek and A Zinetti-Bertschy in Clinical Rehabilitation
Published: 2018
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21. Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort

Author: G. Fond, L. Boyer, F. Schürhoff, F. Berna, O. Godin, E. Bulzacka, M. Andrianarisoa, L. Brunel, B. Aouizerate, D. Capdevielle, I. Chereau, N. Coulon, T. D'Amato, C. Dubertret, J. Dubreucq, C. Faget, C. Lançon, S. Leignier, J. Mallet, D. Misdrahi, C. Passerieux, R. Rey, A. Schandrin, M. Urbach, P. Vidailhet, P.M. Llorca, M. Leboyer, N. Bazin, O. Blanc, I. Chereau-Boudet, G. Chesnoy-Servanin, J.M. Danion, A. Deloge, H. Denizot, J.M. Dorey, C. Fluttaz, S. Fonteneau, F. Gabayet, E. Giraud-Baro, M. Jarroir, D. Lacelle, H. Laouamri, T. Le Gloahec, Y. Le Strat, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, L. Ramet, C. Roman, A. Tessier, A.M. Tronche, F. Vaillant, A. Vehier, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), 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), Les Hôpitaux Universitaires de Strasbourg (HUS), 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, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital Charles Perrens, Université de Bordeaux (UB), Université Montpellier 1 (UM1), Hôpital de la Colombière, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Centre Hospitalier le Vinatier [Bron], 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 de Lyon, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Versailles André Mignot (CHV), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon (CRNL), Centre hospitalier Charles Perrens [Bordeaux], 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), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Alogia, Population, Toxoplasma gondii, Antigens, Protozoan, Inflammation, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Extrapyramidal symptoms, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Prevalence, Humans, Medicine, Cognitive Dysfunction, education, Biological Psychiatry, education.field_of_study, biology, Depression, business.industry, C-reactive protein, medicine.disease, biology.organism_classification, 030227 psychiatry, 3. Good health, Treatment, Psychiatry and Mental health, C-Reactive Protein, Cross-Sectional Studies, Schizophrenia, Immunoglobulin G, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Immunology, Symptoms, biology.protein, Female, Schizophrenic Psychology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, Toxoplasma, Toxoplasmosis, 030217 neurology & neurosurgery
Abstract: Objective Latent Toxoplasma infection has been associated with widespread brain immune activation, increased blood brain barrier permeability, neural disruption, increased dopamine release in dopaminergic neurons, with NMDA activation and with schizophrenia (SZ) onset risk. Toxoplasma has been suggested to be a source of chronic low-grade inflammation and this inflammation has been associated with cognitive impairment in SZ. The objective of the present study were (i) to determine if latent Toxoplasma infection was associated with specific clinical features in stabilized SZ subjects, with cognitive impairment and with increased low-grade peripheral inflammation and (ii) to determine if Treatments with Anti-Toxoplasmic Activity (TATA) were associated with improved outcomes in subjects with latent Toxoplasma infection. Methods A comprehensive 2 daylong clinical and neuropsychological battery was administered in 250 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Solid phase-enzyme microplate immunoassay methods were used to measure IgG class of antibodies to T. gondii in blood sample. Latent Toxoplasma infection was defined by T . gondii IgG ratio ≥0.8, equivalent to ≥10 international units. Chronic peripheral inflammation was defined by highly sensitive C reactive protein blood level ≥ 3 mg/L. Results Latent Toxoplasma infection has been found in 184 (73.6%) of this national multicentric sample. In the multivariate analyses, latent Toxoplasma infection has been significantly associated with higher PANSS negative (aOR = 1.1 [1.1–1.1], p = 0.04) and excitement subscores (aOR = 1.3 [1.1–1.6], p = 0.01), with two specific symptoms (i.e., reference delusion (aOR = 3.6 [1.2–10.6] p = 0.01) and alogia (aOR = 16.7 [2.0–134.7], p = 0.008)) and with chronic low-grade peripheral inflammation (27.2% vs. 7.6%, aOR = 3.8 [1.4–10.3], p = 0.004). Extrapyramidal symptoms remained significantly associated with latent Toxoplasma infection. On the opposite, no significant association of latent Toxoplasma infection with age, gender, age at SZ onset, suicide behavior or cognitive deficits has been found in these models (all p > 0.05). TATA were associated with lower depressive symptoms (aOR = 0.8[0.7–0.9], p = 0.01), and with lower rates of chronic peripheral inflammation (20.9% vs. 48.6%, aOR = 3.5 [1.5–7.9], p = 0.003) but not with higher cognitive scores (p > 0.05). Conclusion The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.
Published: 2018

22. Cigarette smoking and schizophrenia: a specific clinical and therapeutic profile? Results from the FACE-Schizophrenia cohort

Author: J. Mallet, Y. Le Strat, F. Schürhoff, N. Mazer, C. Portalier, M. Andrianarisoa, B. Aouizerate, F. Berna, L. Brunel, D. Capdevielle, I. Chereau, T. D'Amato, H. Denizot, J. Dubreucq, C. Faget, F. Gabayet, C. Lançon, P.M. Llorca, D. Misdrahi, R. Rey, P. Roux, A. Schandrin, M. Urbach, P. Vidailhet, G. Fond, C. Dubertret, N. Bazin, O. Blanc, E. Bulzacka, I. Chereau-Boudet, G. Chesnoy-Servanin, J.M. Danion, A. Deloge, C. Delorme, J.M. Dorey, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, D. Lacelle, H. Laouamri, M. Leboyer, T. Le Gloahec, E. Metairie, I. Offerlin-Meyer, C. Passerieux, P. Peri, S. Pires, L. Ramet, C. Roman, A. Tessier, A.M. Tronche, F. Vaillant, A. Vehier, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), 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), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Montpellier 1 (UM1), Centre Hospitalier le Vinatier [Bron], ONERA - The French Aerospace Lab [Toulouse], ONERA, Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), 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, 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), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Hospitalier d'Annecy, Centre hospitalier d'Annecy, IHU-LIRYC, CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Centre de Psychiatrie et Neurosciences (U894), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-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)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), and Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Population, Comorbidity, Anticholinergic agents, Cigarette Smoking, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Prevalence, medicine, Humans, Antipsychotic, education, Psychiatry, Biological Psychiatry, Clozapine, ComputingMilieux_MISCELLANEOUS, Psychiatric Status Rating Scales, Pharmacology, education.field_of_study, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Confounding, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, medicine.disease, 030227 psychiatry, 3. Good health, Cross-Sectional Studies, Schizophrenia, Multivariate Analysis, Cohort, Educational Status, Female, Aripiprazole, France, Independent Living, business, 030217 neurology & neurosurgery, Antipsychotic Agents, medicine.drug
Abstract: Background Tobacco use is common in patients with schizophrenia (SZ) but little is known on the role of tobacco in the physiopathology or on the course of the disease. Only few studies embrace an extensive examination of clinical and therapeutic characteristics in stabilized patients. The objective of the present study was to determine the prevalence of tobacco smoking in stabilized SZ outpatients and the clinical and treatment characteristics associated with daily tobacco use in a large community-dwelling sample of patients. Methods Three-hundred-and-sixty-one patients were included in the network of the FondaMental Expert Centers for Schizophrenia. Current tobacco status was self-declared. Results 53.7% were smokers. Mean age at tobacco onset was 17.2 years old. In multivariate analyses, after adjustment for confounding factors, positive symptoms and mean daily antipsychotic dose were associated with a higher frequency of tobacco use (OR = 1.06 95%IC[1.02–1.12], for positive symptoms, OR = 1.1, 95%IC[1.02–1.18] for daily antipsychotic dose). Education level, negative symptoms, anticholinergic agents, clozapine or aripiprazole administration were independently associated with a lower frequency of tobacco use (respectively OR = 0.87, 95%IC [0.79, 0.95], OR = 0.95, 95%IC[0.91–0.98], OR = 0.41, 95%IC[0.22–0.76], OR = 0.56, 95%IC = [0.32, 0.99] and OR = 0.49, 95%IC [0.26–0.91]). Conclusion The prevalence of current tobacco smoking in a French community-dwelling SZ patients is higher that observed in the general population. Patients with tobacco use present clinical and therapeutic specificities that may involve interaction between cholinergic-nicotinic and dopaminergic systems. The present study suggests that some therapeutics may improve daily smoking behavior in smokers. These results should be confirmed in longitudinal studies.
Published: 2017

23. Childhood trauma, depression and negative symptoms are independently associated with impaired quality of life in schizophrenia. Results from the national FACE-SZ cohort

Author: M. Andrianarisoa, L. Boyer, O. Godin, L. Brunel, E. Bulzacka, B. Aouizerate, F. Berna, D. Capdevielle, J.M. Dorey, C. Dubertret, J. Dubreucq, C. Faget, F. Gabayet, P.M. Llorca, J. Mallet, D. Misdrahi, R. Rey, R. Richieri, C. Passerieux, A. Schandrin, A.M. Tronche, M. Urbach, P. Vidailhet, F. Schürhoff, G. Fond, O. Blanc, I. Chereau-Boudet, G. Chesnoy-Servanin, J.M. Danion, T. D'Amato, A. Deloge, C. Delorme, H. Denizot, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, M.C. Hardy-Bayle, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, T. Le Gloahec, Y. Le Strat, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, C. Roman, M. Sebilleau, F. Schurhoff, A. Tessier, F. Vaillant, A. Vehier, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, 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 ), 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), Hôpital Charles Perrens, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, 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, Département de psychiatrie adulte, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital La Colombière, 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), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Jeanne d'Arc, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre hospitalier Charles Perrens [Bordeaux], Centre de Psychiatrie et Neurosciences (U894), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital H. Mondor - A. Chenevier, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital Civil de Strasbourg, Neuropsychiatrie : recherche épidémiologique et clinique, Hopital Louis Mourier - AP-HP [Colombes], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Centre Hospitalier de Versailles (CHV), UFR des Sciences de la Santé Simone Veil, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA)
Subjects: Child abuse, Adult, Male, Quality of life, medicine.medical_specialty, Childhood trauma, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, medicine, Humans, Child Abuse, Major depressive episode, Psychiatry, Child, Biological Psychiatry, Depression (differential diagnoses), Psychiatric Status Rating Scales, Positive and Negative Syndrome Scale, Depression, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Multivariate Analysis, Female, Schizophrenic Psychology, Negative symptoms, medicine.symptom, Psychology, 030217 neurology & neurosurgery, Cohort study
Abstract: International audience; OBJECTIVES:Depression and negative symptoms have been associated with impaired Quality of life (QoL) in schizophrenia (SZ). However, childhood trauma may influence both QoL and depression in SZ patients, with consequences for the management of impaired QoL in SZ patients. The aim of the present study was to determine if childhood trauma was associated with impaired QoL in schizophrenia.METHOD:A sample of 544 community-dwelling stabilized SZ patients enrolled in FACE-SZ cohort were utilized in this study (74.1% males, mean aged 32.3years, mean illness duration 10.6years). QoL was self-reported with the S-QoL18 questionnaire. Childhood trauma was self-reported with the Childhood Trauma Questionnaire. Depression was measured by the Calgary Depression Rating Scale for Schizophrenia. Psychotic severity was measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Other clinical factors, treatments, comorbidities, functioning and sociodemographical variables were also recorded, with validated scales.RESULTS:Overall, 151 participants (27.8%) had a current major depressive episode and 406 (82.5%) reported at least one episode of historical childhood trauma. In multivariate analyses, lower QoL total score was associated with a history of childhood trauma (β=-0.21, p
Published: 2017

24. Influence of Venus and Mars in the cognitive sky of schizophrenia. Results from the first-step national FACE-SZ cohort

Author: G. Fond, L. Boyer, M. Leboyer, O. Godin, P.M. Llorca, M. Andrianarisoa, F. Berna, L. Brunel, B. Aouizerate, D. Capdevielle, I. Chereau, T. D'Amato, C. Dubertret, J. Dubreucq, C. Faget, F. Gabayet, J. Mallet, D. Misdrahi, R. Rey, C. Lancon, C. Passerieux, P. Roux, P. Vidailhet, H. Yazbek, F. Schürhoff, E. Bulzacka, O. Blanc, I. Chereau-Boudet, G. Chesnoy-Servanin, Jm Danion, A. Deloge, C. Delorme, H. Denizot, J.M. Dorey, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, M.C. Hardy-Bayle, D. Lacelle, C. Lançon, H. Laouamri, T. Le Gloahec, Y. Le Strat, null Llorca, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, C. Roman, M. Sebilleau, A. Schandrin, F. Schurhoff, A. Tessier, Am Tronche, M. Urbach, F. Vaillant, A. Vehier, E. Vilà, A. Zinetti-Bertschy, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Université Montpellier 1 (UM1), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), ONERA - The French Aerospace Lab [Toulouse], ONERA, Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), 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 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)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], 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), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Hospitalier d'Annecy, Centre hospitalier d'Annecy, IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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), Centre de Psychiatrie et Neurosciences (U894), 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), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, and CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2
Subjects: Adult, Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neuropsychological Tests, Verbal learning, Developmental psychology, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Borderline intellectual functioning, medicine, Verbal fluency test, Humans, Biological Psychiatry, ComputingMilieux_MISCELLANEOUS, Psychiatric Status Rating Scales, Analysis of Variance, Sex Characteristics, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SCCO.NEUR]Cognitive science/Neuroscience, Neuropsychology, Cognitive flexibility, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Cognition, Middle Aged, medicine.disease, Executive functions, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Schizophrenia, Female, Schizophrenic Psychology, Independent Living, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Objectives Sex differences can yield important clues regarding illness pathophysiology and its treatment. Schizophrenia (SZ) has a lower incidence rate, and a better prognosis, in women versus men. The present study investigated the cognitive profiles of both sexes in a large multi-centre sample of community-dwelling SZ patients. Method 544 community-dwelling stable SZ subjects (141 women and 403 men; mean age 34.5 ± 12.1 and 31.6 ± 8.7 years, respectively) were tested with a comprehensive battery of neuropsychological tests. Results Although community-dwelling SZ men had more risk factors for impaired cognition (including first-generation antipsychotics administration and comorbid addictive disorders), women had lower scores on a wide range of cognitive functions, including current and premorbid intellectual functioning, working memory, semantic memory, non-verbal abstract thinking and aspects of visual exploration. However, women scored higher in tests of processing speed and verbal learning, as well as having a lower verbal learning bias. No sex difference were evident for visuospatial learning abilities, cued verbal recall, sustained attention and tests of executive functions, including cognitive flexibility, verbal abstract thinking, verbal fluency and planning abilities. Conclusion Sex differences are evident in the cognitive profiles of SZ patients. The impact on daily functioning and prognosis, as well as longitudinal trajectory, should be further investigated in the FACE-SZ follow-up study. Sex differences in cognition have implications for precision-medicine determined therapeutic strategies. Limits Given the restricted age range of the sample, future research will have to determine cognitive profiles across gender in late onset SZ.
Published: 2017

25. Childhood trauma, dimensions of psychopathology and the clinical expression of bipolar disorders: A pathway analysis

Author: B. Etain, M. Lajnef, C. Henry, V. Aubin, J.M. Azorin, F. Bellivier, T. Bougerol, P. Courtet, S. Gard, J.P. Kahn, C. Passerieux, M. Leboyer, H. Laouamri, K. Souryis, O. Godin, A. Raust, S. Sportiche, P.A. Geoffroy, B. Aouizerate, A. Desage, E. Olie, D. Ducasse, F. Moliere, R. Belzeaux, N. Viglianaise, L. Lescalier, S. Job, R. Cohen, O. Wajsbrot-Elgrabli, M. Polosan, S. Garcon, M.C. Hardy-Bayle, P. Roux, N. Kayser, I. Grevin, J. Loftus, L. Albertini, Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), 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), Hôpital Princesse Grace [Monaco], Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Charles Perrens, Université de Lorraine (UL), Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), King‘s College London, Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Perception et Mémoire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Charles Perrens [Bordeaux], Centre Psychothérapique de Nancy [Laxou] (CPN), FACE-BD Clinical Coordinating Center (FondaMental Foundation), FACE-BD Data Coordinating Center (FondaMental Foundation), FACE-BD Clinical Sites and Principal Collaborators in France, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre Psychothérapique de Nancy (CPN), and roussel, pascale
Subjects: Male, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Poison control, Hostility, Suicide, Attempted, Comorbidity, Childhood trauma, Cohort Studies, 0302 clinical medicine, Emotional abuse, 5. Gender equality, Lability impulsivity, Psychological abuse, Age at onset, Middle Aged, Psychiatry and Mental health, Suicide, Adult Survivors of Child Adverse Events, Female, France, medicine.symptom, Psychology, Clinical psychology, Psychopathology, Adult, medicine.medical_specialty, Substance-Related Disorders, Bipolar disorder, Rapid cycling, Impulsivity, Affect instability, 03 medical and health sciences, Young Adult, Polarity at onset, medicine, Humans, Affective Symptoms, Psychiatry, Substance misuse, Biological Psychiatry, Suicide attempt, Sexual abuse, Sex Offenses, medicine.disease, 030227 psychiatry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Impulsive Behavior, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: This study aims at testing for paths from childhood abuse to clinical indicators of complexity in bipolar disorder (BD), through dimensions of affective dysregulation, impulsivity and hostility. METHOD: 485 euthymic patients with BD from the FACE-BD cohort were included from 2009 to 2014. We collect clinical indicators of complexity/severity: age and polarity at onset, suicide attempt, rapid cycling and substance misuse. Patients completed questionnaires to assess childhood emotional, sexual and physical abuses, affective lability, affect intensity, impulsivity, motor and attitudinal hostility.RESULTS: The path-analysis demonstrated significant associations between emotional abuse and all the affective/impulsive dimensions (p < 0.001). Sexual abuse was moderately associated with emotion-related dimensions but not with impulsivity nor motor hostility. In turn, affect intensity and attitudinal hostility were associated with high risk for lifetime presence of suicide attempts (p < 0.001), whereas impulsivity was associated with a higher risk of lifetime presence of substance misuse (p < 0.001). No major additional paths were identified when including Emotional and Physical Neglect in the model.CONCLUSIONS: This study provides refinement of the links between early adversity, dimensions of psychopathology and the complexity/severity of BD. Mainly, dimensions of affective dysregulation, impulsivity/hostility partially mediate the links between childhood emotional to suicide attempts and substance misuse in BD.
Published: 2017

26. Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset

Author: F. Berna, D. Misdrahi, L. Boyer, B. Aouizerate, L. Brunel, D. Capdevielle, I. Chereau, J.M. Danion, J.M. Dorey, C. Dubertret, J. Dubreucq, C. Faget, F. Gabayet, C. Lancon, J. Mallet, R. Rey, C. Passerieux, A. Schandrin, F. Schurhoff, A.M. Tronche, M. Urbach, P. Vidailhet, P.M. Llorca, G. Fond, O. Blanc, E. Bulzacka, I. Chereau-Boudet, G. Chesnoy-Servanin, T. D'Amato, A. Deloge, C. Delorme, H. Denizot, M. De Pradier, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, M.C. Hardy-Bayle, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, T. Le Gloahec, Y. Le Strat, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, C. Roman, M. Sebilleau, A. Tessier, F. Vaillant, A. Vehier, J. Vilain, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Fondation FondaMental [Créteil], CHU Strasbourg, CHU Bordeaux [Bordeaux], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Charles Perrens, 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), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier le Vinatier [Bron], Université Paris Diderot - Paris 7 (UPD7), Assistance Publique - Hôpitaux de Marseille (APHM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre hospitalier Charles Perrens [Bordeaux], and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Adult, Male, medicine.medical_specialty, Databases, Factual, Psychomotor agitation, medicine.medical_treatment, Schizoaffective disorder, Antidepressant, Akathisia, Severity of Illness Index, Antipsychotic, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Anticholinergic drug, Severity of illness, Prevalence, medicine, Humans, Psychiatry, Psychomotor Agitation, Biological Psychiatry, Benzodiazepine, medicine.disease, 030227 psychiatry, 3. Good health, Barnes Akathisia Scale, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Female, Independent Living, medicine.symptom, Psychology, 030217 neurology & neurosurgery, Antipsychotic Agents
Abstract: International audience; The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.
Published: 2015

27. Metabolic syndrome, abdominal obesity and hyperuricemia in schizophrenia: Results from the FACE-SZ cohort

Author: O. Godin, M. Leboyer, A. Gaman, B. Aouizerate, F. Berna, L. Brunel, D. Capdevielle, I. Chereau, J.M. Dorey, C. Dubertret, J. Dubreucq, C. Faget, F. Gabayet, Y. Le Strat, P.M. Llorca, D. Misdrahi, R. Rey, R. Richieri, C. Passerieux, A. Schandrin, F. Schürhoff, M. Urbach, P. Vidalhet, N. Girerd, G. Fond, O. Blanc, E. Bulzacka, I. Chereau-Boudet, G. Chesnoy-Servanin, J.M. Danion, T. D'Amato, A. Deloge, C. Delorme, H. Denizot, M. Depradier, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, M.C. Hardy-Bayle, D. Lacelle, C. Lançon, H. Laouamri, T. Le Gloahec, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, C. Roman, M. Sebilleau, A. Tessier, A.M. Tronche, F. Vaillant, A. Vehier, P. Vidailhet, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Fondation FondaMental [Créteil], 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), 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, Centre Hospitalier Charles PERRENS, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Hôpital de la Colombière, 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), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier le Vinatier [Bron], 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), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Perrens, Centre Hospitalier de Versailles André Mignot (CHV), 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 d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), AP-HP Hôpital Henri Mondor (Créteil), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital Civil de Strasbourg, Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Hopital Louis Mourier - AP-HP [Colombes], Pôle de Psychiatrie Universitaire Solaris, Marseille, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre Hospitalier de Versailles (CHV), UFR des Sciences de la Santé Simone Veil, Centre d'investigation clinique plurithématique Pierre Drouin (CIC-P), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Psychiatrie et Neurosciences (U894), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Charles Perrens [Bordeaux], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: Male, MESH: Psychiatric Status Rating Scales, MESH: Chi-Square Distribution, Blood Pressure, MESH: Metabolic Diseases, Comorbidity, MESH: Lipoproteins, HDL, Body Mass Index, Cohort Studies, 0302 clinical medicine, Prevalence, Hyperuricemia, MESH: Cohort Studies, Abdominal obesity, Anthropometry, MESH: Blood Pressure, MESH: Hyperuricemia, Metabolic syndrome, 3. Good health, Psychiatry and Mental health, MESH: Young Adult, Obesity, Abdominal, Cohort, Female, France, medicine.symptom, Lipoproteins, HDL, Adult, medicine.medical_specialty, MESH: Obesity, Abdominal, MESH: Body Mass Index, Young Adult, 03 medical and health sciences, Metabolic Diseases, MESH: Anthropometry, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Risk factor, Biological Psychiatry, MESH: Prevalence, Psychiatric Status Rating Scales, Chi-Square Distribution, MESH: Humans, business.industry, MESH: Adult, medicine.disease, MESH: Male, MESH: Schizophrenia, 030227 psychiatry, MESH: France, Endocrinology, Schizophrenia, business, Body mass index, MESH: Female, 030217 neurology & neurosurgery, Dyslipidemia
Abstract: Objective Abdominal obesity was suggested to be a better predictor than Metabolic Syndrome (MetS) for cardiovascular mortality, however this is has not been extensively studied in schizophrenia. Hyperuricemia (HU) was also suggested to be both an independent risk factor for greater somatic comorbidity and a global metabolic stress marker in patients with schizophrenia. The aim of this study was to estimate the prevalence of MetS, abdominal obesity and HU, to examine the association between metabolic parameters with HU in a cohort of French patients with schizophrenia or schizo-affective disorder (SZ), and to estimate the prevalence rates of treatment of cardio-vascular risk factors. Method 240 SZ patients (age = 31.4 years, male gender 74.3%) were systematically included. Metabolic syndrome was defined according to the International Diabetes Federation and HU if serum uric acid level was above 360 μmol/L. Results MetS, abdominal obesity and HU were found respectively in 24.2%, 21.3% and 19.6% of patients. In terms of risk factors, multiple logistic regression showed that after taking into account the potential confounders, the risk for HU was higher in males (OR = 5.9, IC95 [1.7–21.4]) and in subjects with high waist circumference (OR = 3.1, IC95 [1.1–8.3]) or hypertriglyceridemia (OR = 4.9, IC95 [1.9–13]). No association with hypertension, low HDL cholesterol or high fasting glucose was observed. Only 10% of patients with hypertension received a specific treatment, 18% for high fasting glucose and 8% for dyslipidemia. Conclusions The prevalence of MetS, abdominal obesity and hyperuricemia is elevated in French patients with schizophrenia, all of which are considerably under-diagnosed and undertreated. HU is strongly associated with abdominal obesity but not with psychiatric symptomatology.
Published: 2015

28. Improvement of the optical transmission of an eroded soda lime glass by PVB and PES coatings

Author: H. Laouamri, N. Bouaouadja, C. Bousbaa, T. Mahdaoui, and M. A. Madjoubi
Subjects: Soda-lime glass, Polyester, Optical transmission, Materials science, Erosion, Glass, Thin film, Physics and Astronomy(all), Composite material
Abstract: The aim of this work is to improve the optical transmission of a soda lime glass eroded by sandblasting by using polyvinyl butyrate (PVB) and polyester (PES) coatings. Various damage states were obtained in laboratory by varying the projected erodent sand mass (Mp=10–200 g). Transparent layers of PVB and PES were deposited on damaged surfaces. Uncoated eroded glass samples have their optical transmission T strongly deteriorated with the increase of sand mass. It decreases to 27% for a mass of 200 g. The use of the PVB and PES coatings on damaged surface ameliorate substantially the optical transmission. For the extreme case (Mp=200 g), the two deposited layers improve respectively to 87% and 81% with the PVB and the PES films. After a subsequent sandblasting damage on the covered glasses, the evaluation of the optical transmission shows that it only decreases to intermediate values (57% for PVB and 50% for PES).
Published: 2009

29. Treatment with anti-toxoplasmic activity (TATA) for toxoplasma positive patients with bipolar disorders or schizophrenia: a cross-sectional study

Author: Josselin Houenou, José Oliveira, Alexandru Gaman, Guillaume Fond, Philippe Le Corvoisier, Dodji Attiba, Dominique Charron, Nora Hamdani, Rajagopal Krishnamoorthy, Marion Leboyer, Ryad Tamouza, Laurent Boyer, Jean Romain Richard, Marine Delavest, H. Laouamri, Robert H. Yolken, and Faith Dickerson
Subjects: Adult, Male, medicine.medical_specialty, Bipolar Disorder, medicine.drug_class, Cross-sectional study, Antibodies, Protozoan, Schizoaffective disorder, Pharmacology, law.invention, Serology, Young Adult, Randomized controlled trial, law, Internal medicine, Medicine, Humans, Bipolar disorder, Longitudinal Studies, Biological Psychiatry, Psychiatric Status Rating Scales, Psychotropic Drugs, biology, Antiparasitic Agents, business.industry, Toxoplasma gondii, Mood stabilizer, Middle Aged, biology.organism_classification, medicine.disease, Psychiatry and Mental health, Cross-Sectional Studies, Treatment Outcome, Schizophrenia, Female, business, Toxoplasma, Toxoplasmosis
Abstract: The association between Toxoplasma gondii seropositivity and respectively Bipolar Disorder (BD) and Schizophrenia/Schizoaffective disorder (SZ) is one of the most studied link between one pathogen and psychiatric disorders. The aim of the present study was thus to retrospectively determine if the administration of an antipsychotic and/or a mood stabilizer having known in vitro Anti-Toxoplasmic Activity (TATA+) was associated with a better clinical outcome in a population of 152 BD or 114 SZ patients and seropositive for T. gondii infection compared to patients receiving a treatment without anti-toxoplasmic activity (TATA-).This multicenter study was conducted in an academic public hospital during a 3-years period between 2009 and 2011. All consecutive inpatients and outpatients with SZ or BD diagnosis with a stable treatment for more than 4 weeks were recruited. socio-demographic and clinical characteristics measured with validated scales as well as a serological status for toxoplasmic infection were included. Treatments were classified according to their in vitro antitoxoplasmic activity. A multivariate model was used to determine the clinical characteristics that were significantly different between patients receiving a treatment with no antitoxoplasmic activity compared to others.BD patients with positive serum antibodies against T. gondii presented more lifetime depressive episodes (p = 0.048) after adjustment for age, sex and sociodemographic characteristics when treated by drug having no anti-toxo activity, compared to patients having received drugs with anti-toxo activity. A significant difference was not found in BD toxonegative patients and in SZ toxopositive or toxonegative patients.It seems to be of importance to consider prescribing a drug with a clear anti-toxoplasmic activity (TATA+) for BD patients seropositive to T. gondii, in particular valproate that was found as the mood stabilizer with the highest antitoxoplasmic activity. Prospective randomized controlled trials are warranted to confirm this preliminary data.
Published: 2014

30. Psychiatric Co-morbidities in a French Cohort of Adults with High-functioning Autism (HFA)

Author: T. Infor, D. Monnet, Isabelle Scheid, Richard Delorme, Ophélia Godin, Frédérique Amsellem, K. Souyris, Alexandru Gaman, H. Laouamri, J. Houneou, E. Murzi, A. Martinez Teruel, and Marion Leboyer
Subjects: medicine.medical_specialty, 05 social sciences, Cognition, Empathy quotient, medicine.disease, DSM-5, High-functioning autism, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Mood, Autism spectrum disorder, mental disorders, Cohort, medicine, Anxiety, 0501 psychology and cognitive sciences, medicine.symptom, Psychiatry, Psychology, 030217 neurology & neurosurgery, 050104 developmental & child psychology, Clinical psychology
Abstract: Background and rationalePsychiatric comorbidities are shown to be very prevalent in patients diagnosed with Autism Spectrum Disorder (ASD), up high to 53% for mood, 50% anxiety and 43% for ADHD disorders in an European cohort of adults with HFA. Using a new approach, our study proposes to explore aspects of comorbidities in the largest French cohort of HFA adults (C0733/InfoR) by implying qualitative and quantitative clinical tools.AimsTo explore: (1) the prevalence rates of psychiatric comorbidities; (2) the interplay between comorbidities and the ASD symptoms.MethodsDiagnosis was made according to DSM 5 criteria. Dimensional evaluation used Social Responsiveness Scale (SRS), Systemizing Quotient (SQ) and Empathy Quotient (EQ). We used T-test, Mann–Whitney test and linear regression models.ResultsWe included 103 patients (mean age 29.3, sex ratio M/F: 3.4:1). Lifetime prevalence rates of 53.5% for depressive disorder 73.5% for anxiety disorders and 37.5% for ADHD were found. Subjects with psychotic co-morbid symptoms had a more severe social deficit (SRS score 66.2 vs 77.9 P < 0.05); patients with ADHD, lower cognition (mean IQ total 107.7 vs 99.0 P < 0.05). SQs (P < 0.05) were significantly higher in patients with co-morbid psychosis, dysthymia, suicide attempts, and depressive disorders and directly correlated with age (β = 0.35, P < 0.05). SQ and EQ were inversely correlated.DiscussionThe results reproduce the high prevalence of comorbidities in other studies and explore its association with social functioning and cognition. Identification of associated psychiatric conditions in subjects with HFA is therefore a crucial clinical issue potentially guiding the treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Published: 2017

31. The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders

Author: Christopher Gillberg, Hany Goubran-Botros, Thomas Bourgeron, C Boudebesse, Cécile Pagan, H. Laouamri, K. Le Dudal, X Drouot, Jacques Callebert, Frédérique Amsellem, N Ngo-Nguyen, Richard Delorme, Marion Leboyer, and J.M. Launay
Subjects: Adult, Male, Parents, Serotonin, medicine.medical_specialty, Adolescent, Melatonin, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, N-Acetylserotonin, Internal medicine, mental disorders, medicine, Humans, Circadian rhythm, Child, Biological Psychiatry, 030304 developmental biology, 0303 health sciences, Siblings, medicine.disease, Psychiatry and Mental health, Endocrinology, chemistry, Child Development Disorders, Pervasive, Schizophrenia, Autism, Biomarker (medicine), Female, Original Article, Psychopharmacology, Psychology, Biomarkers, 030217 neurology & neurosurgery, Signal Transduction, medicine.drug, Clinical psychology
Abstract: Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35–46%) of patients), as well as the deficit in melatonin (51% (45–57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41–54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS–melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS–melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD.
Published: 2014

32. Key findings on bipolar disorders from the longitudinal FondaMental Advanced Center of Expertise-Bipolar Disorder (FACE-BD) cohort.

Author: Leboyer M, Godin O, Llorca PM, Aubin V, Bellivier F, Belzeaux R, Courtet P, Costagliola D, Dubertret C, M'Bailara K, Haffen E, Henry C, Laouamri H, Passerieux C, Pelletier A, Polosan M, Roux P, Schwan R, Samalin L, Olié E, and Etain B
Subjects: Anxiety Disorders epidemiology, Cohort Studies, Comorbidity, Humans, Suicide, Attempted psychology, Bipolar Disorder diagnosis, Bipolar Disorder epidemiology, Bipolar Disorder therapy
Abstract: Background: The FACE-BD cohort is an observational cohort of individuals with bipolar disorders (BD) who benefited from a systematic evaluation with evidence-based treatment recommendations and who were followed-up every year for 3 years in France. The objectives were to describe the lifetime course of BD, associated psychiatric and somatic comorbidities, and cognition profile. This cohort aims to identify clinical/biological signatures of outcomes, trajectories of functioning and transition between clinical stages. This article summarizes 10 years of findings of the FACE-BD cohort., Method & Results: We included 4422 individuals, all having a baseline assessment, among which 61.2% had at least one follow-up visit at either one, two or three years. A subsample of 1200 individuals had at least one biological sample (serum, plasma, DNA). Assessments include family history of psychiatric disorders, psychiatric diagnosis, current mood symptoms, functioning, hospitalizations, suicidal attempts, physical health, routine blood tests, treatment history, psychological dimensions, medico-economic data and a cognitive assessment. Studies from this cohort illustrate that individuals with BD display multiple coexistent psychiatric associated conditions including sleep disturbances, anxiety disorders, substance use disorders and suicide attempts as well as a high prevalence of metabolic syndrome. During follow-up, we observed a 55% reduction of the number of days of hospitalization and a significant improvement in functioning., Conclusions: The FACE-BD cohort provides a strong research infrastructure for clinical research in BD and has a unique position among international cohorts because of its comprehensive clinical assessment and sustainable funding from the French Ministry of Health., (Copyright © 2022. Published by Elsevier B.V.)
Published: 2022
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33. Direct medical cost of bipolar disorder: Insights from the FACE-BD longitudinal cohort.

Author: Laidi C, Godin O, Etain B, Bellivier F, Elandaloussi Y, Olié E, Aouizerate B, Gard S, Loftus J, Belzeaux R, Dubertret C, Laouamri H, Passerieux C, Pelletier A, Polosan M, Schwan R, Samalin L, Llorca PM, Courtet P, Durand-Zaleski I, and Leboyer M
Subjects: Cohort Studies, Cost-Benefit Analysis, Health Care Costs, Humans, Bipolar Disorder epidemiology
Abstract: Background: Bipolar disorder (BD) is a severe chronic psychiatric disorder affecting 0.5 to 1% of the population worldwide. To date, most studies have estimated the cost of BD via information sourced from insurance claims with limited information on clinical characteristics and course of BD. The aims of this study are (i) to estimate the direct healthcare cost associated with BD and to identify contributing factors and (ii) to study the evolution of cost during a two-year follow-up period., Method: We analyzed a sample of 1116 individuals with BD included in the Advanced Centers of Expertise in Bipolar Disorder cohort. We estimated the direct healthcare cost per year and per patient, and we identified the clinical features of patients with BD associated with higher direct healthcare costs. In a subsample of patients followed up for two years centers of expertise for BD, we studied the evolution of direct healthcare cost., Results: The average cost of bipolar disorder was € 6910 per year and per patient. Clinical features of BD, sociodemographic characteristics, and associated addiction were associated with higher direct healthcare costs. In the subsample of patients followed-up for two years, direct healthcare cost dropped by more than 50%, strongly suggesting the beneficial effect of specialized care organization., Limitation: We did not estimate indirect healthcare and intangible costs., Conclusion: Our study investigates the cost of BD and its evolution in a deeply phenotyped longitudinal sample. Cost-utility and cost-effectiveness analyses are required to inform resource allocation decisions and to promote innovative healthcare organizations., (Copyright © 2022. Published by Elsevier B.V.)
Published: 2022
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34. The puzzle of quality of life in schizophrenia: putting the pieces together with the FACE-SZ cohort.

Author: Ehrminger M, Roux P, Urbach M, André M, Aouizerate B, Berna F, Bohec AL, Capdevielle D, Chéreau I, Clauss J, Dubertret C, Dubreucq J, Fond G, Honciuc RM, Lançon C, Laouamri H, Leigner S, Mallet J, Misdrahi D, Pignon B, Rey R, Schürhoff F, Passerieux C, and Brunet-Gouet E
Subjects: Cohort Studies, Cross-Sectional Studies, Humans, Quality of Life psychology, Schizophrenic Psychology, Schizophrenia complications
Abstract: Background: The determinants of quality of life (QoL) in schizophrenia are largely debated, mainly due to methodological discrepancies and divergence about the concepts concerned. As most studies have investigated bi- or tri-variate models, a multivariate model accounting for simultaneous potential mediations is necessary to have a comprehensive view of the determinants of QOL. We sought to estimate the associations between cognitive reserve, cognition, functioning, insight, depression, schizophrenic symptoms, and QoL in schizophrenia and their potential mediation relationships., Methods: We used structural equation modeling with mediation analyses to test a model based on existing literature in a sample of 776 patients with schizophrenia from the FondaMental Foundation FACE-SZ cohort., Results: Our model showed a good fit to the data. We found better functioning to be positively associated with a better QoL, whereas better cognition, better insight, higher levels of depression, and schizophrenic symptoms were associated with a lower QoL in our sample. Cognitive reserve is not directly linked to QoL, but indirectly in a negative manner via cognition. We confirm the negative relationship between cognition and subjective QoL which was previously evidenced by other studies; moreover, this relationship seems to be robust as it survived in our multivariate model. It was not explained by insight as some suggested, thus the mechanism at stake remains to be explained., Conclusion: The pathways to subjective QoL in schizophrenia are complex and the determinants largely influence each other. Longitudinal studies are warranted to confirm these cross-sectional findings.
Published: 2022
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35. Overlap and Mutual Distinctions Between Clinical Recovery and Personal Recovery in People With Schizophrenia in a One-Year Study.

Author: Dubreucq J, Gabayet F, Godin O, Andre M, Aouizerate B, Capdevielle D, Chereau I, Clauss-Kobayashi J, Coulon N, D'Amato T, Dorey JM, Dubertret C, Faraldo M, Laouamri H, Leigner S, Lancon C, Leboyer M, Llorca PM, Mallet J, Misdrahi D, Passerieux C, Rey R, Pignon B, Schorr B, Urbach M, Schürhoff F, Szoke A, Fond G, and Berna F
Subjects: Adult, Analysis of Variance, Chi-Square Distribution, Female, Humans, Male, Schizophrenia physiopathology, Quality of Life psychology, Recovery of Function physiology, Schizophrenia therapy
Abstract: Recovery is a multidimensional construct that can be defined either from a clinical perspective or from a consumer-focused one, as a self-broadening process aimed at living a meaningful life beyond mental illness. We aimed to longitudinally examine the overlap and mutual distinctions between clinical and personal recovery. Of 1239 people with schizophrenia consecutively recruited from the FondaMental Advanced Centers of Expertise for SZ network, the 507 present at one-year did not differ from those lost to follow-up. Clinical recovery was defined as the combination of clinical remission and functional remission. Personal recovery was defined as being in the rebuilding or in the growth stage of the Stages of Recovery Instrument (STORI). Full recovery was defined as the combination of clinical recovery and personal recovery. First, we examined the factors at baseline associated with each aspect of recovery. Then, we conducted multivariable models on the correlates of stable clinical recovery, stable personal recovery, and stable full recovery after one year. At baseline, clinical recovery and personal recovery were characterized by distinct patterns of outcome (i.e. better objective outcomes but no difference in subjective outcomes for clinical recovery, the opposite pattern for personal recovery, and better overall outcomes for full recovery). We found that clinical recovery and personal recovery predicted each other over time (baseline personal recovery for stable clinical recovery at one year; P = .026, OR = 4.94 [1.30-23.0]; baseline clinical recovery for stable personal recovery at one year; P = .016, OR = 3.64 [1.31-11.2]). In short, given the interaction but also the degree of difference between clinical recovery and personal recovery, psychosocial treatment should target, beyond clinical recovery, subjective aspects such as personal recovery and depression to reach full recovery., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Published: 2022
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36. Immune Signatures of Treatment-Resistant Schizophrenia: A FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) Study.

Author: Leboyer M, Godin O, Terro E, Boukouaci W, Lu CL, Andre M, Aouizerate B, Berna F, Barau C, Capdevielle D, Clauss-Kobayashi J, Chereau I, D Amato T, Dubertret C, Dubreucq J, Fond G, Laouamri H, Leignier S, Lancon C, Llorca PM, Mallet J, Le Corvoisier P, Misdrahi D, Passerieux C, Rey R, Pignon B, Urbach M, Szoke A, Schürhoff F, and Tamouza R
Abstract: Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics., (© The Author(s) 2021. Published by Oxford University Press on behalf of the University of Maryland’s school of medicine, Maryland Psychiatric Research Center.)
Published: 2021
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37. Precision psychiatry with immunological and cognitive biomarkers: a multi-domain prediction for the diagnosis of bipolar disorder or schizophrenia using machine learning.

Author: Fernandes BS, Karmakar C, Tamouza R, Tran T, Yearwood J, Hamdani N, Laouamri H, Richard JR, Yolken R, Berk M, Venkatesh S, and Leboyer M
Subjects: Biomarkers, Cognition, Humans, Machine Learning, Neuropsychological Tests, Bipolar Disorder diagnosis, Psychiatry, Schizophrenia diagnosis
Abstract: Precision psychiatry is attracting increasing attention lately as a recognized priority. One of the goals of precision psychiatry is to develop tools capable of aiding a clinically informed psychiatric diagnosis objectively. Cognitive, inflammatory and immunological factors are altered in both bipolar disorder (BD) and schizophrenia (SZ), however, most of these alterations do not respect diagnostic boundaries from a phenomenological perspective and possess great variability in different individuals with the same phenotypic diagnosis and, consequently, none so far has proven to have the ability of reliably aiding in the differential diagnosis of BD and SZ. We developed a probabilistic multi-domain data integration model consisting of immune and inflammatory biomarkers in peripheral blood and cognitive biomarkers using machine learning to predict diagnosis of BD and SZ. A total of 416 participants, being 323, 372, and 279 subjects for blood, cognition and combined biomarkers analysis, respectively. Our multi-domain model performances for the BD vs. control (sensitivity 80% and specificity 71%) and for the SZ vs. control (sensitivity 84% and specificity 81%) pairs were high in general, however, our multi-domain model had only moderate performance for the differential diagnosis of BD and SZ (sensitivity 71% and specificity 73%). In conclusion, our results show that the diagnosis of BD and of SZ, and that the differential diagnosis of BD and SZ can be predicted with possible clinical utility by a computational machine learning algorithm employing blood and cognitive biomarkers, and that their integration in a multi-domain outperforms algorithms based in only one domain. Independent studies are needed to validate these findings.
Published: 2020
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38. Immunoglobulin sub-class distribution in bipolar disorder and schizophrenia: potential relationship with latent Toxoplasma Gondii infection.

Author: Hamdani N, Bengoufa D, Godin O, Doukhan R, Le Guen E, Daban-Huard C, Bennabi M, Delavest M, Lépine JP, Boukouaci W, Laouamri H, Houenou J, Jamain S, Richard JR, Lecorvosier P, Yolken R, Rajagopal K, Leboyer M, and Tamouza R
Subjects: Adult, Case-Control Studies, Female, Humans, Male, Middle Aged, Risk Factors, Toxoplasma immunology, Toxoplasmosis complications, Young Adult, Bipolar Disorder immunology, Bipolar Disorder parasitology, Immunoglobulins blood, Schizophrenia immunology, Schizophrenia parasitology, Toxoplasmosis immunology
Abstract: Background: Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection., Methods: 334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ., Results: Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls., Conclusions: Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.
Published: 2018
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39. Effects of Cumulative Herpesviridae and Toxoplasma gondii Infections on Cognitive Function in Healthy, Bipolar, and Schizophrenia Subjects.

Author: Hamdani N, Daban-Huard C, Godin O, Laouamri H, Jamain S, Attiba D, Delavest M, Lépine JP, Le Corvoisier P, Houenou J, Richard JR, Yolken RH, Krishnamoorthy R, Tamouza R, Leboyer M, and Dickerson FB
Subjects: Adult, Comorbidity, Cross-Sectional Studies, Female, France, Humans, Male, Middle Aged, Neuropsychological Tests statistics & numerical data, Psychiatric Status Rating Scales, Psychometrics statistics & numerical data, Reference Values, Risk Factors, Bipolar Disorder diagnosis, Bipolar Disorder epidemiology, Cognitive Dysfunction diagnosis, Cognitive Dysfunction epidemiology, Encephalitis, Herpes Simplex diagnosis, Encephalitis, Herpes Simplex epidemiology, Schizophrenia diagnosis, Schizophrenia epidemiology, Toxoplasmosis, Cerebral diagnosis, Toxoplasmosis, Cerebral epidemiology
Abstract: Objective: Schizophrenia and bipolar disorder are associated with cognitive impairment leading to social disruption. While previous studies have focused on the effect of individual infectious exposure, namely, Herpesviridae viruses or Toxoplasma gondii (T gondii), on cognitive functioning, the objective of the present study was to examine the effect of multiple infections on cognitive functioning in patients with schizophrenia and bipolar disorder and in healthy controls., Methods: Seropositivity to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV), and T gondii was related to cognitive status among 423 participants (recruited between 2008 and 2014; 138 patients with bipolar disorder, 105 patients with schizophrenia [DSM-IV criteria], and 180 healthy controls) for episodic verbal memory (California Verbal Learning Test), working memory (Wechsler Adult Intelligence Scale, third edition), and premorbid intelligence quotient (National Adult Reading Test)., Results: Seropositivity to and antibody levels of HSV-1 were significantly associated with working memory, which persisted after correction (backward digit span: β = -0.10 [0.05], χ² = 33.89, P = .0001) in the overall sample. This association was particularly strong in the control group (β = -0.18 [0.08], P = .04, Z = -3.55, P = .0008; corrected P = .012). Further, cumulative exposure to HSV-1, HSV-2, and CMV viruses and T gondii parasite was also associated with lower scores on working memory as measured by backward digit span in the overall sample (Z = 2.86, P = .004; Z = 2.47, P = .01; and Z = 3.35, P = .01, respectively)., Conclusions: Exposures to Herpesviridae and T gondii parasite seem to impact cognitive functioning. Because infections caused by Herpesviridae and/or T gondii parasite are quite common in the (general) population, assessing and confirming the cognitive impairment among those who have cumulative exposures is useful and of interest., (© Copyright 2016 Physicians Postgraduate Press, Inc.)
Published: 2017
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40. Differential effects of childhood trauma and cannabis use disorders in patients suffering from schizophrenia.

Author: Baudin G, Godin O, Lajnef M, Aouizerate B, Berna F, Brunel L, Capdevielle D, Chereau I, Dorey JM, Dubertret C, Dubreucq J, Faget C, Fond G, Gabayet F, Laouamri H, Lancon C, Le Strat Y, Tronche AM, Misdrahi D, Rey R, Passerieux C, Schandrin A, Urbach M, Vidalhet P, Llorca PM, and Schürhoff F
Subjects: Adult, Age of Onset, Female, Humans, Male, Psychiatric Status Rating Scales, Psychotic Disorders psychology, Schizophrenic Psychology, Stress, Psychological complications, Adult Survivors of Child Adverse Events psychology, Marijuana Abuse complications, Marijuana Abuse psychology, Psychotic Disorders complications, Schizophrenia complications
Abstract: Background: Childhood trauma (CT) and cannabis use are both environmental and modifier risk factors for schizophrenia. However, little is known about how they interact in schizophrenia. We examined the main effect of each of these two environmental factors on the clinical expression of the disease using a large set of variables, and we tested whether and how cannabis and CT interact to influence the course and the presentation of the illness., Methods: A sample of 366 patients who met the DSM-IV-TR criteria for schizophrenia was recruited through the FACE-SCZ (Fondamental Advanced Centre of Expertise - Schizophrenia) network. Patients completed a large standardized clinical evaluation including Structured Clinical Interview for DSM Disorders-I (SCID-I), Positive and Negative Symptoms Scale (PANSS), Columbia-Suicide Severity Rating Scale (C-SSRS), Global Assessment of Functioning (GAF), Short-Quality of Life-18 (S-QoL-18), and Medication Adherence Rating Scale (MARS). We assessed CT with the Childhood Trauma Questionnaire and cannabis status with SCID-I., Results: CT significantly predicted the number of hospitalizations, GAF, and S-QoL-18 scores, as well as the PANSS total, positive, excitement, and emotional distress scores. Cannabis use disorders significantly predicted age of onset, and MARS. There was no significant interaction between CT and cannabis use disorders. However, we found evidence of a correlation between these two risk factors., Conclusions: CT and cannabis both have differential deleterious effects on clinical and functional outcomes in patients with schizophrenia. Our results highlight the need to systematically assess the presence of these risk factors and adopt suitable therapeutic interventions., (Copyright © 2016 Elsevier B.V. All rights reserved.)
Published: 2016
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41. Medication and aggressiveness in real-world schizophrenia. Results from the FACE-SZ dataset.

Author: Fond G, Boyer L, Favez M, Brunel L, Aouizerate B, Berna F, Capdevielle D, Chereau I, Dorey JM, Dubertret C, Dubreucq, Faget C, Gabayet F, Laouamri H, Lancon C, Le Strat Y, Misdrahi D, Rey R, Passerieux C, Schandrin A, Schurhoff F, Tronche AM, Urbach M, Vidalhet P, Llorca PM, and Pelissolo A
Subjects: Adult, Aggression psychology, Antipsychotic Agents adverse effects, Benzodiazepines adverse effects, Cohort Studies, Cross-Sectional Studies, Diagnostic and Statistical Manual of Mental Disorders, Female, France epidemiology, Humans, Male, Middle Aged, Psychotic Disorders epidemiology, Psychotic Disorders psychology, Schizophrenia epidemiology, Schizophrenic Psychology, Surveys and Questionnaires, Young Adult, Aggression drug effects, Antipsychotic Agents therapeutic use, Benzodiazepines therapeutic use, Databases, Factual trends, Psychotic Disorders drug therapy, Schizophrenia drug therapy
Abstract: Introduction: The primary objective of this study was to determine if second-generation antipsychotic (SGA) administration was associated with lower aggressiveness scores compared to first-generation (FGA) in schizophrenia (SZ). The secondary objective was to determine if antidepressants, mood stabilizers, and benzodiazepines administration were respectively associated with lower aggressiveness scores compared to patients who were not administered these medications., Methods: Three hundred thirty-one patients with schizophrenia (N = 255) or schizoaffective disorder (N = 76) (mean age = 32.5 years, 75.5 % male gender) were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with the structured clinical interview for DSM-IV Axis I disorders and validated scales for psychotic symptomatology, insight, and compliance. Aggressiveness was measured by the Buss-Perry Aggression Questionnaire (BPAQ) score. Ongoing psychotropic treatment was recorded., Results: Patients who received SGA had lower BPAQ scores than patients who did not (p = 0.01). More specifically, these patients had lower physical and verbal aggression scores. On the contrary, patients who received benzodiazepines had higher BPAQ scores than patients who did not (p = 0.04). No significant difference was found between BPAQ scores of patients respectively being administered mood stabilizers (including valproate), antidepressant, and the patients who were not. These results were found independently of socio-demographical variables, psychotic symptomatology, insight, compliance into treatment, daily-administered antipsychotic dose, the way of antipsychotic administration (oral vs long acting), current alcohol disorder, and daily cannabis consumption., Conclusion: The results of the present study are in favor of the choice of SGA in SZ patients with aggressiveness, but these results need further investigation in longitudinal studies. Given the potent side effects of benzodiazepines (especially dependency and cognitive impairment) and the results of the present study, their long-term prescription is not recommended in patients with schizophrenia and aggressive behavior.
Published: 2016
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42. Treatment with anti-toxoplasmic activity (TATA) for toxoplasma positive patients with bipolar disorders or schizophrenia: a cross-sectional study.

Author: Fond G, Boyer L, Gaman A, Laouamri H, Attiba D, Richard JR, Delavest M, Houenou J, Le Corvoisier P, Charron D, Krishnamoorthy R, Oliveira J, Tamouza R, Yolken R, Dickerson F, Leboyer M, and Hamdani N
Subjects: Adult, Antibodies, Protozoan blood, Bipolar Disorder drug therapy, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Middle Aged, Psychiatric Status Rating Scales, Schizophrenia drug therapy, Toxoplasma immunology, Toxoplasmosis complications, Treatment Outcome, Young Adult, Antiparasitic Agents therapeutic use, Bipolar Disorder complications, Psychotropic Drugs therapeutic use, Schizophrenia complications, Toxoplasmosis drug therapy
Abstract: Objective: The association between Toxoplasma gondii seropositivity and respectively Bipolar Disorder (BD) and Schizophrenia/Schizoaffective disorder (SZ) is one of the most studied link between one pathogen and psychiatric disorders. The aim of the present study was thus to retrospectively determine if the administration of an antipsychotic and/or a mood stabilizer having known in vitro Anti-Toxoplasmic Activity (TATA+) was associated with a better clinical outcome in a population of 152 BD or 114 SZ patients and seropositive for T. gondii infection compared to patients receiving a treatment without anti-toxoplasmic activity (TATA-)., Methods: This multicenter study was conducted in an academic public hospital during a 3-years period between 2009 and 2011. All consecutive inpatients and outpatients with SZ or BD diagnosis with a stable treatment for more than 4 weeks were recruited. socio-demographic and clinical characteristics measured with validated scales as well as a serological status for toxoplasmic infection were included. Treatments were classified according to their in vitro antitoxoplasmic activity. A multivariate model was used to determine the clinical characteristics that were significantly different between patients receiving a treatment with no antitoxoplasmic activity compared to others., Results: BD patients with positive serum antibodies against T. gondii presented more lifetime depressive episodes (p = 0.048) after adjustment for age, sex and sociodemographic characteristics when treated by drug having no anti-toxo activity, compared to patients having received drugs with anti-toxo activity. A significant difference was not found in BD toxonegative patients and in SZ toxopositive or toxonegative patients., Conclusions: It seems to be of importance to consider prescribing a drug with a clear anti-toxoplasmic activity (TATA+) for BD patients seropositive to T. gondii, in particular valproate that was found as the mood stabilizer with the highest antitoxoplasmic activity. Prospective randomized controlled trials are warranted to confirm this preliminary data., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
Published: 2015
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43. The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders.

Author: Pagan C, Delorme R, Callebert J, Goubran-Botros H, Amsellem F, Drouot X, Boudebesse C, Le Dudal K, Ngo-Nguyen N, Laouamri H, Gillberg C, Leboyer M, Bourgeron T, and Launay JM
Subjects: Adolescent, Adult, Biomarkers blood, Child, Child Development Disorders, Pervasive genetics, Female, Humans, Male, Parents, Siblings, Child Development Disorders, Pervasive blood, Melatonin blood, Serotonin analogs & derivatives, Serotonin blood, Signal Transduction physiology
Abstract: Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35-46%) of patients), as well as the deficit in melatonin (51% (45-57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41-54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS-melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS-melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD.
Published: 2014
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