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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. 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

5. 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

6. 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

7. 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

8. 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

9. 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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10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. Nicotine dependence is associated with depression and childhood trauma in smokers with schizophrenia: results from the FACE-SZ dataset.

Author

Rey R, D'Amato T, Boyer L, Brunel L, Aouizerate B, Berna F, Capdevielle D, Chereau I, Chesnoy-Servanin G, Denizot H, Dorey JM, Dubertret C, Dubreucq J, Faget C, Gabayet F, Lancon C, Mallet J, Misdrahi D, Passerieux C, Schandrin A, Schürhoff F, Urbach M, Vidailhet P, Llorca PM, and Fond G

Subjects
Adult, Comorbidity, Female, Humans, Male, Sex Factors, Young Adult, Adult Survivors of Child Adverse Events statistics & numerical data, Depression epidemiology, Schizophrenia epidemiology, Smoking epidemiology, Tobacco Use Disorder epidemiology
Abstract

In a perspective of personalized care for smoking cessation, a better clinical characterization of smokers with schizophrenia (SZ) is needed. The objective of this study was to determine the clinical characteristics of SZ smokers with severe nicotine (NIC) dependence. 240 stabilized community-dwelling SZ smokers (mean age = 31.9 years, 80.4% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and assessed with validated scales. Severe NIC dependence was defined by a Fagerstrom questionnaire score ≥ 7. Depression was defined by a Calgary score ≥ 6. Childhood trauma was self-reported by the Childhood Trauma Questionnaire score (CTQ). Ongoing psychotropic treatment was recorded. Severe NIC dependence was identified in 83 subjects (34.6%), depression in 60 (26.3%). 44 (22.3%) subjects were treated by antidepressants. In a multivariate model, severe NIC dependence remained associated with depression (OR = 3.2, p = 0.006), male gender (OR = 4.5, p = 0.009) and more slightly with childhood trauma (OR = 1.03, p = 0.044), independently of socio-demographic characteristics, psychotic symptoms severity, psychotropic treatments and alcohol disorder. NIC dependence was independently and strongly associated with, respectively, depression and male gender in schizophrenia, and only slightly with history of childhood trauma. Based on these results, the care of both nicotine dependence and depression should be evaluated for an effective smoking cessation intervention in schizophrenia.

Published
2017
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17. Chronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset.

Author

Bulzacka E, Boyer L, Schürhoff F, Godin O, Berna F, Brunel L, Andrianarisoa M, Aouizerate B, Capdevielle D, Chéreau-Boudet I, Chesnoy-Servanin G, Danion JM, Dubertret C, Dubreucq J, Faget C, Gabayet F, Le Gloahec T, Llorca PM, Mallet J, Misdrahi D, Rey R, Richieri R, Passerieux C, Roux P, Yazbek H, Leboyer M, and Fond G

Subjects
Adult, Chronic Disease, Cognitive Dysfunction etiology, Female, Humans, Male, Middle Aged, Schizophrenia complications, C-Reactive Protein analysis, Cognitive Dysfunction blood, Cognitive Dysfunction physiopathology, Inflammation blood, Schizophrenia blood
Abstract

Objectives: Inflammation, measured by abnormal blood C-reactive protein (CRP) level, has been described in schizophrenia (SZ), being inconsistently related to impaired cognitive functions. The aim of the present study is to investigate cognitive impairment associated with abnormal CRP levels in a large multi-centric sample of community-dwelling SZ patients, using a comprehensive neuropsychological battery., Method: Three hundred sixty-nine community-dwelling stable SZ subjects (76.2% men, mean age 32.7 y) were included and tested with a comprehensive battery of neuropsychological tests. Abnormal CRP level was defined as >3mg/L., Results: Multiple factor analysis revealed that abnormal CRP levels, found in 104 patients (28.2%), were associated with impaired General Intellectual Ability and Abstract Reasoning (aOR = 0.56, 95% CI 0.35-0.90, P = .014), independently of age, sex, education level, psychotic symptomatology, treatments, and addiction comorbidities. Abnormal CRP levels were also associated with the decline of all components of working memory (respectively effect size [ES] = 0.25, P = .033; ES = 0.27, P = .04; ES = 0.33, P = .006; and ES = 0.38, P = .004) and a wide range of other impaired cognitive functions, including memory (ES = 0.26, P = .026), learning abilities (ES = 0.28, P = .035), semantic memory (ES = 0.26, P = .026), mental flexibility (ES = 0.26, P = .044), visual attention (ES = 0.23, P = .004) and speed of processing (ES = 0.23, P = .043)., Conclusion: Our results suggest that abnormal CRP level is associated with cognitive impairment in SZ. Evaluating the effectiveness of neuroprotective anti-inflammatory strategies is needed in order to prevent cognitive impairment in SZ., (© The Author 2016. 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
2016
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18. «Cognitus & Moi»: A Computer-Based Cognitive Remediation Program for Children with Intellectual Disability.

Author

Demily C, Rigard C, Peyroux E, Chesnoy-Servanin G, Morel A, and Franck N

Abstract

Attentional, visuospatial, and social cognition deficits have a negative impact on children's adaptative and social competences and, as a result, on their ability to achieve a normal functioning and behavior. Until now and despite the frequency of those deficits, there is a lack of children's specific cognitive remediation tools specifically dedicated to attentional and visuospatial areas. The «Cognitus & Moi» program involves a variety of exercises in a paper and/or pencil (n = 30) or a computerized format (n = 29) and a strategy coaching approach. Each module of «Cognitus & Moi» targets a single impaired cognitive area, within the limits of cognitive domains' overlapping. The little cartoon character named Cognitus, who illustrates the program, is supposed to be very friendly and kind toward children. Cognitus will accompany them throughout the program for an effective and positive reinforcement. The main goal of «Cognitus & Moi» is to adjust to children's difficulties in daily life. Moreover, since the cognitive remediation benefit is complex to apply in daily life, the program is based on a metacognitive strategy. After a complete neuropsychological assessment and a psychoeducational session (with the child and the parents), 16 1-h-sessions of cognitive remediation with the therapist are proposed. Each session is composed of three parts: (1) computerized tasks focusing on specific attentional or visuospatial components (20 min). The attentional module targets hearing, visual, and divided attention. A double attention task is also proposed. The visuospatial module targets eye tracking and gaze direction, spatial orientation, visuospatial memory and construction, and mental imagery; (2) pen and paper tasks focusing on the same processes (20 min) and a facial emotion recognition task; (3) a proposal of a home-based task (during 20 min). Weekly, specific attentional and visuospatial home tasks are proposed to the child and analyzed with the parents and the therapist. Indeed, home exercises are useful to promote the transfer of strategies to daily life and their subsequent automation. The heterogeneity of cognitive deficits in intellectual deficiency necessitates an individualized cognitive remediation therapy. In this regard, «Cognitus & Moi» seems to be a promising tool.

Published
2016
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19. From Theory to PrACTice: A Cognitive Remediation Program Based on a Neuropsychological Model of Schizophrenia.

Author

Fabre D, Vehier A, Chesnoy-Servanin G, Gouiller N, D'Amato T, and Saoud M

Abstract

Cognitive dysfunction is one of the hallmark deficits of schizophrenia. A wide range of studies illustrate how it is strongly interconnected to clinical presentation and daily life functioning [see Ref. (1, 2)]. Hence, cognition is an important treatment target in schizophrenia. To address the challenge of cognitive enhancement in schizophrenia, a large number of cognitive remediation programs have been developed and evaluated over the past several decades. First, an overview of these programs is presented highlighting their specificity to cognitive deficit in schizophrenia using an integrated method. In this case, cognitive training focuses on enhancing several elementary cognitive functions considered as a prerequisite to social skills or vocational training modules. These programs are based on the neurodevelopmental hypothesis of schizophrenia. However, moderate improvement for patients who benefit from these therapies has been observed as described in Wykes et al. review (3). Next, neuropsychological models of schizophrenia are then presented. They highlight the critical role of the internally generated intentions in appropriate willful actions. The cognitive control mechanism deals with this ability. Interestingly, available cognitive remediation programs have not been influenced by these models. Hence, we propose another alternative to set up a specific cognitive remediation program for schizophrenia patients by targeting the cognitive control mechanism. We describe the PrACTice program that is in the process of being validated.

Published
2015
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20. Complex phenotype with social communication disorder caused by mosaic supernumerary ring chromosome 19p.

Author

Demily C, Rossi M, Chesnoy-Servanin G, Martin B, Poisson A, Sanlaville D, and Edery P

Subjects
Adult, Communication Disorders pathology, Humans, Male, Mosaicism, Phenotype, Ring Chromosomes, Chromosomes, Human, Pair 19 genetics, Communication Disorders genetics, Trisomy
Abstract

Background: Deletions or duplications of chromosome 19 are rare and there is no previous report in the literature of a ring chromosome derived from proximal 19p. Copy Number Variants (CNVs) responsible for complex phenotypes with Social Communication Disorder (SCD), may contribute to improve knowledge about the distinction between intellectual deficiency and autism spectrum disorders., Case Presentation: We report the clinical and cytogenetic characterization of a patient (male, 33 years-old, first child of healthy Portuguese non-consanguineous parents) presenting with a complex phenotype including SCD without intellectual deficiency and carrying a mosaic supernumerary ring chromosome 19p. Microarray-Based Comparative Genomic Hybridization and Fluorescence in situ Hybridization were performed. Genetic analysis showed a large mosaic interstitial duplication 19p13.12p12 of the short arm of chromosome 19, spanning 8.35 Mb. Our data suggested a putative association between psychosocial dysfunction and mosaic pure trisomy 19p13.2p12., Conclusion: This clinical report demonstrated the need to analyze more discreet trait-based subsets of complex phenotypes to improve the ability to detect genetic effects. To address this question and the broader issue of deciphering the yet unknown genetic contributors to complex phenotype with SCD, we suggest performing systematic psychological and psychiatric assessments in patients with chromosomal abnormalities.

Published
2014
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