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1. 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
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2. Structural topology defines protective CD8 + T cell epitopes in the HIV proteome

Author

David R. Collins, Michael T. Waring, Gaurav D. Gaiha, Olivia Mae Waring, Todd M. Allen, Bruce D. Walker, Karen A. Power, Jonathan M. Urbach, Musie Ghebremichael, Daniel P Worrall, Elizabeth J. Rossin, James Chodosh, Itai Muzhingi, Chioma Nwonu, Melis N. Anahtar, Christian Landeros, Alicja Piechocka-Trocha, and Ruchi M. Newman

Subjects
0301 basic medicine, Multidisciplinary, Immunogen, T cell, Human leukocyte antigen, Biology, Topology, Epitope, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Immune system, 030220 oncology & carcinogenesis, medicine, Cytotoxic T cell, HIV vaccine, CD8
Abstract

Structure-based immunogen design Vaccine design for highly mutable pathogens is hindered by a paucity of conserved immunogenic epitopes. Gaiha et al. employed a structure-based technique using network theory to assign scores to protein structure in order to infer mutational constraints (see the Perspective by McMichael and Carrington). The authors validated the method on proteins with published functional outcomes and then assessed mutational constraints within the HIV proteome. Highly networked residues strongly associated with immune control of HIV infection and may lead to protective immunogens for pathogens for which there is currently no efficient vaccine. Science , this issue p. 480 ; see also p. 438

Published
2019
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3. 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
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4. Functional impairment of HIV-specific CD8+ T cells precedes aborted spontaneous control of viremia

Author

Xiao-Dong Lian, Umar Arshad, Bruce D. Walker, Jonathan M. Urbach, Adrienne G. Yanez, Todd M. Allen, David R. Collins, Michael J. Peluso, Ngoc L. Ly, Ruchi M. Newman, Anna Rull, Yelizaveta Rassadkina, Xu G. Yu, Zachary J. Racenet, Gaurav D. Gaiha, Karen A. Power, Francesc Vidal, Geetha H. Mylvaganam, Steven G. Deeks, and Mathias Lichterfeld

Subjects
Adult, Male, Immunology, HIV Infections, Viremia, CD8-Positive T-Lymphocytes, Biology, Article, Virus, Recurrence, medicine, Humans, Immunology and Allergy, Cytotoxic T cell, Transcription factor, virus diseases, Middle Aged, Cell cycle, medicine.disease, Cytolysis, Infectious Diseases, KLF2, Female, CD8
Abstract

Summary Spontaneous control of HIV infection has been repeatedly linked to antiviral CD8+ T cells but is not always permanent. To address mechanisms of durable and aborted control of viremia, we evaluated immunologic and virologic parameters longitudinally among 34 HIV-infected subjects with differential outcomes. Despite sustained recognition of autologous virus, HIV-specific proliferative and cytolytic T cell effector functions became selectively and intrinsically impaired prior to aborted control. Longitudinal transcriptomic profiling of functionally impaired HIV-specific CD8+ T cells revealed altered expression of genes related to activation, cytokine-mediated signaling, and cell cycle regulation, including increased expression of the antiproliferative transcription factor KLF2 but not of genes associated with canonical exhaustion. Lymphoid HIV-specific CD8+ T cells also exhibited poor functionality during aborted control relative to durable control. Our results identify selective functional impairment of HIV-specific CD8+ T cells as prognostic of impending aborted HIV control, with implications for clinical monitoring and immunotherapeutic strategies.

Published
2021
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5. Comparison of three scales (BIS, SUMD and BCIS) for measuring insight dimensions and their evolution after one-year of follow-up: Findings from the FACE-SZ Cohort

Author

Delphine Capdevielle, Joanna Norton, Bruno Aouizerate, Fabrice Berna, Isabelle Chereau, Thierry D'Amato, Caroline Dubertret, Julien Dubreucq, Guillaume Fond, Lançon C, Jasmina Mallet, David Misdrahi, Catherine Passerieux, Romain Rey, Franck Schurhoff, Mathieu Urbach, Pierre-Michel Llorca, Stéphane Raffard, B. Aouizerate, F. Berna, O. Blanc, D. Capdevielle, I. Chereau-Boudet, N. Coulon, T. D'Amato, J.M. Dorey, C. Dubertret, G. Fond, F. Gabayet, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, P.M. Llorca, J. Mallet, E. Metairie, D. Misdrahi, C. Passerieux, B. Pignon, P. Peri, C. Portalier, R. Rey, C. Roman, F. Schürhoff, A. Szöke, M. Urbach, A. Zinetti-Bertschy, Fondation FondaMental [Créteil], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Bordeaux [Bordeaux], Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Neuropsychologie Cognitive et Physiophatologie de la Schizophrénie (Inserm U1114 - UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, CHU Clermont-Ferrand, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paul-Valéry - Montpellier 3 (UPVM), This work was funded by AP-HP (Assistance Publique des Hôpitaux de Paris), Fondation FondaMental (RTRS Santé Mentale), by the Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01, and by INSERM (Institut National de la Santé et de la Recherche Médicale)., Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Centre de recherche en neurosciences de Lyon (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Psychometrics, Composite score, [SDV]Life Sciences [q-bio], Clinical state, Cognitive Insight, 03 medical and health sciences, Cognitive dimensions of notations, 0302 clinical medicine, medicine, Humans, Biological Psychiatry, Psychiatric Status Rating Scales, Cognition, Awareness, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Psychotic Disorders, Clinical Insight, Schizophrenia, Cohort, Schizophrenic Psychology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Insight, Psychology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Treatment need, Clinical psychology
Abstract

International audience; The aim of our study was to compare the performance of three different instruments measuring clinical and cognitive dimensions of insight. Data on 182 outpatients with schizophrenia and one-year follow-up assessments was drawn from the FACE-SZ cohort. Awareness of clinical state (« clinical insight ») was measured using both a clinician-rated measure (the Scale to assess Unawareness of Mental Disorder (SUMD)), and a self-report measure (the Birchwood Insight Scale (BIS). Cognitive insight was measured using a self-report measure (the Beck Cognitive Insight Scale (BCIS)). For each scale, change in insight was examined at the follow-up. Correlations between SUMD and BIS subscales measuring same dimensions were significant. BIS-BCIS correlations were weak for all combinations except between BIS illness dimension and BCIS composite score. At the follow-up, BIS and SUMD awareness of treatment need improved whereas illness and symptom awareness increased only on the SUMD. Conversely, cognitive insight composite scores decreased. Despite relatively good overall agreement between the two clinical insight instruments, considerable variability for similar insight dimensions measured by different instruments was found. Agreement between cognitive and clinical insight is moderate. Our study strengthens the argument that insight is harder to operationalize than other symptoms and may explain why it is so seldom explicitly targeted in schizophrenia treatment.

Published
2021
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6. The gender gap in critical care task force participation

Author

Kealy R. Ham, Haley M Urbach, Katherine Janssen, Sara E Erickson, Colin R. Cooke, Sandi S. Wewerka, and Peter B. Bach

Subjects
Pulmonary and Respiratory Medicine, Gerontology, Male, Critical Care, business.industry, Task force, Extramural, Advisory Committees, MEDLINE, Physicians, Women, Sex Factors, Sex factors, Medicine, Humans, Female, Gender gap, business
Published
2019

7. 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
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8. 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
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9. 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
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10. Relationships between low-grade peripheral inflammation and psychotropic drugs in schizophrenia: results from the national FACE-SZ cohort

Author

G, Fond, N, Resseguier, F, Schürhoff, O, Godin, M, Andrianarisoa, L, Brunel, E, Bulzacka, B, Aouizerate, F, Berna, D, Capdevielle, I, Chereau, T, D'Amato, C, Dubertret, J, Dubreucq, C, Faget, F, Gabayet, C, Lançon, P M, Llorca, J, Mallet, D, Misdrahi, C, Passerieux, R, Rey, A, Schandrin, M, Urbach, P, Vidailhet, L, Boyer, M, Leboyer, 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), Université de Montpellier (UM), 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]), 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, and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Male, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Pharmacology, Overweight, Cohort Studies, 0302 clinical medicine, Antimanic Agents, Hypnotics and Sedatives, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, General Medicine, Middle Aged, 16. Peace & justice, Antidepressive Agents, 3. Good health, Psychiatry and Mental health, Psychotropic drug, C-Reactive Protein, Schizophrenia, Cohort, Aripiprazole, Female, France, medicine.symptom, medicine.drug, Antipsychotic Agents, Adult, medicine.medical_specialty, 03 medical and health sciences, Young Adult, Sex Factors, Internal medicine, medicine, Humans, Antipsychotic, Biological Psychiatry, Inflammation, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, 030227 psychiatry, Psychotic Disorders, Quetiapine, business, Body mass index, 030217 neurology & neurosurgery
Abstract

Low-grade inflammation has repeatedly been associated with schizophrenia (SZ) and in particular with cognitive impairment. Female gender, overweight and tobacco smoking have been suggested as risk factors to increase inflammation while preclinical inconsistent findings have been found regarding the association with psychotropic drugs. The aim of this study was to explore if psychotropic drugs were associated with inflammation in SZ and to determine which psychotropic drug was associated with inflammation in stable SZ subjects while considering clinical confounding factors. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. High-sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. The zero-inflated Poisson regression model estimated the relationship between low-grade inflammation and psychotropic drug. Four hundred and five stabilized, community-dwelling SZ subjects (mean age = 32.6 years, 74% male gender) have been included. In total, 148 participants (36.5%) were found with undetectable blood hs-CRP level. The probability of having an undetectable CRP was associated with a lower body mass index (p 0.0001) and no cyamemazine add-on antipsychotic therapy (p = 0.001). The other 257 participants (63.5%) were found to have low-grade inflammation (hs-CRP 0 mg/L). Low-grade inflammation was significantly associated with female gender (p = 0.004), higher body mass index (p 0.0001), current tobacco smoking (p 0.0001), clomipramine (p = 0.04), quetiapine (p 0.0001) and hypnotic (p = 0.0006) consumption while decreased hs-CRP blood levels was associated with aripiprazole (p = 0.004) and valproate/valpromide (p = 0.03) consumption. The present study suggests that some psychotropic drugs (quetiapine, cyamemazine, clomipramine) may be associated with increased peripheral low-grade inflammation in SZ patients while others (aripiprazole, valproate) may be associated with decreased peripheral low-grade inflammation. These results should be replicated in SZ and non-SZ populations and the biological underpinnings should be further explored.

Published
2018
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11. 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
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12. 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
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13. 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
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14. 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
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15. 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
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16. 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
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17. Modeling Microbial Virulence in a Genomic Era: Impact of Shared Genomic Tools and Data Sets

Author

Nicole T. Liberati, Jonathan M. Urbach, M. Ausubel Frederick, Daniel G. Lee, and Gang Wu

Subjects
Research groups, Host (biology), business.industry, Pseudomonas aeruginosa, Mutant, Virulence, Context (language use), Computational biology, Biology, medicine.disease_cause, Biotechnology, medicine, business, Gene, Pathogen
Abstract

This chapter discusses the relevance of model host pathogenesis as a third general approach to studying microbial virulence, in which infections are studied in the context of nonvertebrate whole animal hosts. The chapter explains the combination of four key steps: (i) the development of the model host-pathogen system, (ii) the development of genomic tools in both the pathogen and host, (iii) the distribution and use of these tools by the greater research community beyond the laboratories involved in their initial development, and (iv) the collection and ultimate integration of experimental data from a wide variety of research groups made possible by the widespread use of a common resource and its accompanying Web-accessible public database. Pseudomonas aeruginosa PA14 was chosen for the construction of a non-redundant mutant library because it is remarkably virulent in the greatest number of model hosts tested, as well as in a number of murine systems of infection. There are four major advantages to construction of a non-redundant mutant library approach as opposed to the traditional approach of screening a random collection of strains for avirulent or attenuated mutants. A microarray experiment in a Caenhorhabidits elegans mutant defective in a newly defined host defense response gene identified candidate downstream genes important in the response to pathogens.

Published
2014
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18. Combining Genomic Tools to Dissect Multifactorial Virulence in Pseudomonas aeruginosa

Author

Nicole T. Liberati, Gang Wu, Frederick M. Ausubel, Jonathan M. Urbach, Daniel G. Lee, and Rhonda L. Feinbaum

Subjects
Genetics, Pseudomonas aeruginosa, Virulence, Human pathogen, Bacterial genome size, biochemical phenomena, metabolism, and nutrition, Biology, bacterial infections and mycoses, medicine.disease_cause, Pathogenicity island, Microbiology, medicine, ORFS, Gene, Genotyping
Abstract

The growing number of sequenced bacterial genomes, including those of important pathogenic isolates, has made a significant impact on the field of bacterial pathogenesis (Raskin et al., 2006). Combined with other technical advances in the laboratory, this wealth of information has made possible the development and widespread adoption of genomic tools for the study of infectious disease. This chapter focuses on the sequencing and functional analysis of PA14, a clinical isolate of the ubiquitous environmental bacterium and important opportunistic human pathogen, Pseudomonas aeruginosa. By comparing PA14 to the sequence of the less virulent P. aeruginosa isolate, PAO1, we have identified genomic sequences absent in one or the other strain in order to examine the relationship between genomic content and pathogenicity. To assess the importance of strain-specific genes and virulence, we tested 20 diverse P. aeruginosa strains, including PA14 and PAO1, in a Caenorhabdidits elegans pathogenesis model and observed a wide range of pathogenic potential; however, genotyping these strains using a custom microarray showed that the presence of genes present in PA14 and absent in PAO1 did not correlate with the virulence of these strains. To further examine the roles in virulence of PA14 genes absent in PAO1, we utilized a full-genome non-redundant mutant library of PA14 to identify five ORFs (absent in PAO1) required for C. elegans killing. Surprisingly, although these five genes are present in many other P. aeruginosa strains, they do not correlate with virulence in C. elegans. Genes required for pathogenicity in one strain are neither required for nor predictive of virulence in other strains. We therefore propose that virulence in this organism is a complex process that is both multifactorial and combinatorial. Not only are multiple pathogenicity determinants acting in parallel within a given strain, but also, when comparing different strains, different combinations of pathogenicity factors may be selected to determine the ultimate virulence

Published
2008
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19. Correction for Kulesekara et al., Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Author

Nicole T. Liberati, Frederick M. Ausubel, Mamoru Hyodo, Anja Brencic, Hemantha Kulasakara, Jonathan M. Urbach, Daniel G. Lee, Vincent T. Lee, Stephen Lory, Alice N. Neely, Yoshihiro Hayakawa, and Sachiko Miyata

Subjects
Cyclic gmp, Multidisciplinary, Pseudomonas aeruginosa, medicine, Virulence, Phosphodiesterase, Biology, medicine.disease_cause, Corrections, Microbiology
Abstract

microbiology . For the article “Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence,” by Hemantha Kulesekara, Vincent …

Published
2006

20. Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Author

Yoshihiro Hayakawa, Frederick M. Ausubel, Nicole T. Liberati, Anja Brencic, Alice N. Neely, Daniel G. Lee, Vincent T. Lee, Jonathan M. Urbach, Sachiko Miyata, Stephen Lory, Mamoru Hyodo, and Hemantha Kulesekara

Subjects
Cyclic di-GMP, Diguanylate cyclase activity, Virulence, Biology, medicine.disease_cause, Microbiology, chemistry.chemical_compound, Bacterial Proteins, medicine, Pseudomonas Infections, Gene, Cyclic GMP, Genetics, Multidisciplinary, Pseudomonas aeruginosa, Phosphoric Diester Hydrolases, Escherichia coli Proteins, Genomics, GGDEF domain, Biological Sciences, Protein Structure, Tertiary, PilZ domain, Phenotype, chemistry, Genes, Bacterial, Biofilms, Mutation, biology.protein, Diguanylate cyclase, Phosphorus-Oxygen Lyases, Genome, Bacterial
Abstract

The opportunistic pathogen Pseudomonas aeruginosa is responsible for systemic infections in immunocompromised individuals and chronic respiratory disease in patients with cystic fibrosis. Cyclic nucleotides are known to play a variety of roles in the regulation of virulence-related factors in pathogenic bacteria. A set of P. aeruginosa genes, encoding proteins that contain putative domains characteristic of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs) that are responsible for the maintenance of cellular levels of the second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) was identified in the annotated genomes of P. aeruginosa strains PAO1 and PA14. Although the majority of these genes are components of the P. aeruginosa core genome, several are located on presumptive horizontally acquired genomic islands. A comprehensive analysis of P. aeruginosa genes encoding the enzymes of c-di-GMP metabolism (DGC- and PDE-encoding genes) was carried out to analyze the function of c-di-GMP in two disease-related phenomena, cytotoxicity and biofilm formation. Analysis of the phenotypes of DGC and PDE mutants and overexpressing clones revealed that certain virulence-associated traits are controlled by multiple DGCs and PDEs through alterations in c-di-GMP levels. A set of mutants in selected DGC- and PDE-encoding genes exhibited attenuated virulence in a mouse infection model. Given that insertions in different DGC and PDE genes result in distinct phenotypes, it seems likely that the formation or degradation of c-di-GMP by these enzymes is in highly localized and intimately linked to particular targets of c-di-GMP action.

Published
2006

21. The broad host range pathogen Pseudomonas aeruginosa strain PA14 carries two pathogenicity islands harboring plant and animal virulence genes

Author

Regina L. Baldini, Daniel G. Lee, Jianxin He, Maude Saucier, Nicole T. Liberati, Jonathan M. Urbach, Laurence G. Rahme, Qunhao Zhang, Eric Déziel, and Howard M. Goodman

Subjects
Arabidopsis, Virulence, Biology, medicine.disease_cause, Microbiology, Mice, Open Reading Frames, Gene cluster, medicine, Animals, Pseudomonas Infections, ORFS, Pathogen, Plant Diseases, Sequence Deletion, Genetics, Multidisciplinary, Pseudomonas aeruginosa, Biological Sciences, Pathogenicity island, Bacterial adhesin, Plant Leaves, Disease Models, Animal, Mobile genetic elements
Abstract

The ubiquitous bacterium Pseudomonas aeruginosa is the quintessential opportunistic pathogen. Certain isolates infect a broad range of host organisms, from plants to humans. The pathogenic promiscuity of particular variants may reflect an increased virulence gene repertoire beyond the core P. aeruginosa genome. We have identified and characterized two P. aeruginosa pathogenicity islands (PAPI-1 and PAPI-2) in the genome of PA14, a highly virulent clinical isolate. The 108-kb PAPI-1 and 11-kb PAPI-2, which are absent from the less virulent reference strain PAO1, exhibit highly modular structures, revealing their complex derivations from a wide array of bacterial species and mobile elements. Most of the genes within these islands that are homologous to known genes occur in other human and plant bacterial pathogens. For example, PAPI-1 carries a complete gene cluster predicted to encode a type IV group B pilus, a well known adhesin absent from strain PAO1. However, >80% of the PAPI-1 DNA sequence is unique, and 75 of its 115 predicted ORF products are unrelated to any known proteins or functional domains. Significantly, many PAPI-1 ORFs also occur in several P. aeruginosa cystic fibrosis isolates. Twenty-three PAPI ORFs were mutated, and 19 were found to be necessary for full plant or animal virulence, with 11 required for both. The large set of “extra” virulence functions encoded by both PAPIs may contribute to the increased promiscuity of highly virulent P. aeruginosa strains, by directing additional pathogenic functions.

Published
2004

22. Genome-Wide Identification of Pseudomonas aeruginosa Virulence-Related Genes Using a Caenorhabditis elegans Infection Model

Author

Allison L. Adonizio, Jonathan M. Urbach, Slavica Djonovic, Anne-Ruxandra Carvunis, Frederick M. Ausubel, Nicole T. Liberati, and Rhonda L. Feinbaum

Subjects
Genetic Screens, Operon, Pathogenesis, medicine.disease_cause, Genome, Gram Negative, Genomic library, lcsh:QH301-705.5, Caenorhabditis elegans, Genetics, 0303 health sciences, Animal Models, Bacterial Pathogens, Host-Pathogen Interaction, Pseudomonas aeruginosa, Prokaryotic Models, Research Article, lcsh:Immunologic diseases. Allergy, Virulence Factors, Immunology, Virulence, Biology, Microbiology, 03 medical and health sciences, Model Organisms, Bacterial Proteins, Virology, medicine, Animals, Pseudomonas Infections, Microbial Pathogens, Molecular Biology, Gene, Gene Library, 030304 developmental biology, Evolutionary Biology, Bacterial Evolution, 030306 microbiology, Bacteriology, biology.organism_classification, lcsh:Biology (General), Microbial Evolution, Parasitology, lcsh:RC581-607, Genome, Bacterial, Genetic screen
Abstract

Pseudomonas aeruginosa strain PA14 is an opportunistic human pathogen capable of infecting a wide range of organisms including the nematode Caenorhabditis elegans. We used a non-redundant transposon mutant library consisting of 5,850 clones corresponding to 75% of the total and approximately 80% of the non-essential PA14 ORFs to carry out a genome-wide screen for attenuation of PA14 virulence in C. elegans. We defined a functionally diverse 180 mutant set (representing 170 unique genes) necessary for normal levels of virulence that included both known and novel virulence factors. Seven previously uncharacterized virulence genes (ABC transporters PchH and PchI, aminopeptidase PepP, ATPase/molecular chaperone ClpA, cold shock domain protein PA0456, putative enoyl-CoA hydratase/isomerase PA0745, and putative transcriptional regulator PA14_27700) were characterized with respect to pigment production and motility and all but one of these mutants exhibited pleiotropic defects in addition to their avirulent phenotype. We examined the collection of genes required for normal levels of PA14 virulence with respect to occurrence in P. aeruginosa strain-specific genomic regions, location on putative and known genomic islands, and phylogenetic distribution across prokaryotes. Genes predominantly contributing to virulence in C. elegans showed neither a bias for strain-specific regions of the P. aeruginosa genome nor for putatively horizontally transferred genomic islands. Instead, within the collection of virulence-related PA14 genes, there was an overrepresentation of genes with a broad phylogenetic distribution that also occur with high frequency in many prokaryotic clades, suggesting that in aggregate the genes required for PA14 virulence in C. elegans are biased towards evolutionarily conserved genes., Author Summary Pseudomonas aeruginosa is an opportunistic human pathogen that can also infect a wide range of model organisms, including the nematode Caenorhabditis elegans. To identify P. aeruginosa genes that play key roles in the pathogenic process, we performed a screen for mutants that exhibited reduced ability to kill C. elegans using a previously constructed non-redundant library representing approximately 80% of the non-essential P. aeruginosa PA14 genes. We defined a functionally diverse set of 180 P. aeruginosa mutants (representing 170 unique genes) necessary for normal levels of virulence that included both known and novel virulence factors. The major contributors to P. aeruginosa virulence in the C. elegans infection model were not secretion systems or their corresponding effectors, but rather regulators (particularly ones that are involved in quorum sensing) and genes likely to play key roles in survival of P. aeruginosa within the host intestine. Moreover, these putative P. aeruginosa virulence genes are neither overrepresented in strain-specific regions nor in horizontally acquired genomic islands and furthermore tend to have orthologs that are widely distributed across sequenced prokaryotic species. These data underscore the diversity of pathways involved in virulence, and especially the importance of highly conserved genes for P. aeruginosa virulence in the C. elegans host model.

Published
2012
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23. Isomerization of all-trans-retinoic acid to 9-cis-retinoic acid

Author

Robert R. Rando and Jonathan M. Urbach

Subjects
Stereochemistry, Retinoic acid, Tretinoin, Buffers, Biochemistry, chemistry.chemical_compound, Isomerism, medicine, Animals, Molecular Biology, Chromatography, High Pressure Liquid, chemistry.chemical_classification, Retinol, Biological activity, Cell Biology, Kinetics, Membrane, chemistry, Liver, Microsome, Thiol, Microsomes, Liver, Cattle, Isomerization, medicine.drug, Subcellular Fractions, Research Article
Abstract

The discovery of the biological activity of 9-cis-retinoic acid raises questions as to its mode of biosynthesis. A simple mechanism involves the direct isomerization of all-trans-retinoic acid to 9-cis-retinoic acid. It is shown here that bovine liver membranes, but not supernatant fractions, can isomerize all-trans-retinoic acid into 9-cis-retinoic acid and 13-cis-retinoic acid. The concentration of 9-cis-retinoic acid generated approaches its equilibrium concentration, which is determined here to be approximately 15%. However, the isomerization process could not be shown to be saturable, and is first-order in all-trans-retinoic acid in the concentration range measured (8.3 nM to 3 microM). Isomerization reactions measured using bovine liver microsomes appear to be mediated by thiol groups, as they can be blocked by group-specific thiol-blocking reagents such as N-ethylmaleimide. It is interesting to note that the non-stereospecific behaviour observed here mimics what is observed when all-trans-retinoic acid is applied to cells. Finally, significant formation of 9-cis-retinoids was not found when the reaction was carried out with liver microsomes and either all-trans-retinol or all-trans-retinal.

Published
1994

24. [Untitled]

Author

Raju Kucherlapati, Jianxin He, Nicole T. Liberati, Lenard T Diggins, Gang Wu, George Grills, Eric Déziel, Lisa Friedman, Li Li, Rhonda L. Feinbaum, Frederick M. Ausubel, Laurence G. Rahme, Kate Montgomery, Jonathan M. Urbach, Maude Saucier, Daniel G. Lee, and Sachiko Miyata

Subjects
Genetics, 0303 health sciences, biology, 030306 microbiology, Sequence analysis, Pseudomonas aeruginosa, Virulence, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, biology.organism_classification, medicine.disease_cause, Pathogenicity island, Genome, Bacterial genetics, 03 medical and health sciences, medicine, Gene, Caenorhabditis elegans, 030304 developmental biology
Abstract

Background: Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important opportunistic human pathogen. Generally, the acquisition of genes in the form of pathogenicity islands distinguishes pathogenic isolates from nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa, PA14, and compared it with a previously sequenced (and less pathogenic) strain, PAO1, to identify novel virulence genes. Results: The PA14 and PAO1 genomes are remarkably similar, although PA14 has a slightly larger genome (6.5 megabses [Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are absent in PAO1 to determine which of these genes, if any, contribute to its enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we tested 18 additional diverse strains in the C. elegans model and observed a wide range of pathogenic potential; however, genotyping these strains using a custom microarray showed that the presence of PA14 genes that are absent in PAO1 did not correlate with the virulence of these strains. Second, we utilized a full-genome nonredundant mutant library of PA14 to identify five genes (absent in PAO1) required for C. elegans killing. Surprisingly, although these five genes are present in many other P. aeruginosa strains, they do not correlate with virulence in C. elegans. Conclusion: Genes required for pathogenicity in one strain of P. aeruginosa are neither required for nor predictive of virulence in other strains. We therefore propose that virulence in this organism is both multifactorial and combinatorial, the result of a pool of pathogenicity-related genes that interact in various combinations in different genetic backgrounds.

Published
2006
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25. Thiol dependent isomerization of all-trans-retinoic acid to 9-cis-retinoic acid

Author

Robert R. Rando and Jonathan M. Urbach

Subjects
Isomerization, medicine.drug_class, Stereochemistry, Radical, Biophysics, Retinoic acid, Tretinoin, Ascorbic Acid, Biochemistry, chemistry.chemical_compound, Isomerism, Thiol radical, Structural Biology, Genetics, medicine, Animals, Vitamin E, Retinoid, Sulfhydryl Compounds, Bovine serum albumin, Molecular Biology, chemistry.chemical_classification, biology, Cell Biology, Free Radical Scavengers, Ascorbic acid, chemistry, biology.protein, Thiol, Microsomes, Liver, Cattle, medicine.drug
Abstract

The important biological effector 9-cis-retinoic acid can be generated by liver microsomes or by bovine serum albumin in detergent. The mechanism of this isomerization reaction is the subject of these studies. The protein mediated isomerization process is shown to be thiol- and pH-dependent. Moreover, the retinoic acids are also isomerized by 1-dodecanethiol in the presence of detergents. This isomerization process is pH-dependent as well, with isomerization rates increasing with pH. The isomerization reactions are quenched with free radical traps, such as α-tocopherol and ascorbic acid, suggesting that a thiol radical mechanism, rather than a thiolate anion-dependent mechanism, is implicated here. The pH dependence can be understood in terms of a thiol radical mechanism, because thiol radicals are produced from thiolate anions in the presence of oxygen. The facile thiol-mediated isomerization of the retinoic acids suggests that this could be a physiologically relevant mechanism for the formation of 9-cis-retinoic acid from all-trans-retinoic acid.

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26. Anaesthesia for day-care surgery: a symposium (II)

Author

Gerald Edelist and G. M. Urbach

Subjects
Ontario, Washington, medicine.medical_specialty, Day care surgery, Outpatient Clinics, Hospital, business.industry, Surgicenters, Pain medicine, Minor surgical procedure, Hospital unit, General Medicine, Anesthesiology and Pain Medicine, Ambulatory Surgical Procedures, Anesthesia, Anesthesiology, Humans, Medicine, business, Surgery Department, Hospital
Abstract

The organization of three main types of out-patient anaesthesia facility are discussed. These are the hospital unit with independent facilities, the integrated hospital unit and the independent out-patient surgical centre. The use of an out-patient facility for minor surgical procedures has been suggested as a less expensive alternative to in-patient management. Some of the advantages and disadvantages are outlined.

Published
1980
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