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1. Medical comorbidities in bipolar disorder (BIPCOM): clinical validation of risk factors and biomarkers to improve prevention and treatment. Study protocol

Author: Giovanni de Girolamo, Ole A. Andreassen, Michael Bauer, Paolo Brambilla, Stefano Calza, Nicholas Citerà, Rosa Corcoy, Andrea Fagiolini, Miguel Garcia-Argibay, Ophélia Godin, Florian Klingler, Nene F. Kobayashi, Henrik Larsson, Marion Leboyer, Silke Matura, Alessandra Martinelli, Víctor De la Peña-Arteaga, Roberto Poli, Andreas Reif, Philipp Ritter, Linn N. Rødevand, Marta Magno, Elisa Caselani, and for the BIPCOM consortium
Subjects: Bipolar disorder, Metabolic syndrome, Medical comorbidities, Quality of life, Precision medicine, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Abstract: Abstract Background BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities. Methods The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology. Discussion BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases. Trial registration: ISRCTN68010602 at https://www.isrctn.com/ISRCTN68010602 . Registration date: 18/04/2023.
Published: 2024
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2. Decreased telomere length in a subgroup of young individuals with bipolar disorders: replication in the FACE-BD cohort and association with the shelterin component POT1

Author: Luana Spano, Cynthia Marie-Claire, Ophélia Godin, Apolline Lebras, Cindie Courtin, Jean-Louis Laplanche, Marion Leboyer, Bruno Aouizerate, Antoine Lefrere, Raoul Belzeaux, Philippe Courtet, Emilie Olié, Caroline Dubertret, Raymund Schwan, Valérie Aubin, Paul Roux, Mircea Polosan, Ludovic Samalin, Emmanuel Haffen, Fondamental Advanced Centers Of Expertise In Bipolar Disorders (Face-Bd) Collaborators, Frank Bellivier, and Bruno Etain
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Bipolar disorder (BD) has been associated with premature cellular aging with shortened telomere length (TL) as compared to the general population. We recently identified a subgroup of young individuals with prematurely shortened TL. The aims of the present study were to replicate this observation in a larger sample and analyze the expression levels of genes associated with age or TL in a subsample of these individuals. TL was measured on peripheral blood DNA using quantitative polymerase chain reaction in a sample of 542 individuals with BD and clustering analyses were performed. Gene expression level of 29 genes, associated with aging or with telomere maintenance, was analyzed in RNA samples from a subsample of 129 individuals. Clustering analyses identified a group of young individuals (mean age 29.64 years), with shorter TL. None of the tested clinical variables were significantly associated with this subgroup. Gene expression level analyses showed significant downregulation of MYC, POT1, and CD27 in the prematurely aged young individuals compared to the young individuals with longer TL. After adjustment only POT1 remained significantly differentially expressed between the two groups of young individuals. This study confirms the existence of a subgroup of young individuals with BD with shortened TL. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.
Published: 2024
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3. The cost of illness and burden of suicide and suicide attempts in France

Author: Laeticia Blampain Segar, Charles Laidi, Ophélia Godin, Philippe Courtet, Guillaume Vaiva, Marion Leboyer, and Isabelle Durand-Zaleski
Subjects: Suicide, Suicide attempts, Health economics, Cost, Death, Disability, Psychiatry, RC435-571
Abstract: Abstract Background With 11,558 deaths and 200,000 suicide attempts in 2019, France is among the European countries most affected. The aim of this study was to determine the costs and burden of suicides and suicide attempts in France (population 67 million). Methods We estimated direct costs, comprising healthcare, as well as post-mortem costs including autopsy, body removal, funeral expenses, police intervention and support groups; indirect costs comprised lost productivity, daily allowances; the burden of disease calculations used a monetary value for death and disability based on incidence data. Data was obtained from the national statistics, health and social care database, registries, global burden of disease, supplemented by expert opinion. We combined top down and bottom up approaches. Results The total costs and burden of suicides and suicide attempts was estimated at €18.5 billion and €5.4 billion, respectively. Direct costs were €566 million and €75 million; indirect costs were €3.8 billion and €3.5 billion; monetary value for death and disability was €14.6 billion and €1.3. The monetary value for death and disability represented 79.1% and 24.8% of total costs for suicide and suicide attempt respectively. Some costs were based upon expert opinion, caregivers’ burden was not counted and pre COVID data only is reported. Conclusions In France, the total cost and burden of suicides and suicide attempts was several billion €, suggesting major potential savings from public health interventions.
Published: 2024
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4. Predictors of medication adherence in a large 1-year prospective cohort of individuals with schizophrenia: insights from the multicentric FACE-SZ dataset

Author: David Misdrahi, Maud Dupuy, Yecodji Dansou, Laurent Boyer, Fabrice Berna, Delphine Capdevielle, Isabelle Chereau, Nathalie Coulon, Thierry D’Amato, Caroline Dubertret, Sylvain Leignier, Pierre Michel Llorca, Christophe Lançon, Jasmina Mallet, Christine Passerieux, Baptiste Pignon, Romain Rey, Franck Schürhoff, Joel Swendsen, Mathieu Urbach, Andrei Szöke, Ophélia Godin, Guillaume Fond, and the FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) Group
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Schizophrenia is characterized by the most salient medication adherence problems among severe mental disorders, but limited prospective data are available to predict and improve adherence in this population. This investigation aims to identify predictors of medication adherence over a 1-year period in a large national cohort using clustering analysis. Outpatients were recruited from ten Schizophrenia Expert Centers and were evaluated with a day-long standardized battery including clinician and patient-rated medication adherence measures. A two-step cluster analysis and multivariate logistic regression were conducted to identify medication adherence profiles based on the Medication Adherence rating Scale (MARS) and baseline predictors. A total of 485 participants were included in the study and medication adherence was significantly improved at the 1-year follow-up. Higher depressive scores, lower insight, history of suicide attempt, younger age and alcohol use disorder were all associated with poorer adherence at 1 year. Among the 203 patients with initially poor adherence, 86 (42%) switched to good adherence at the 1-year follow-up, whereas 117 patients (58%) remained poorly adherent. Targeting younger patients with low insight, history of suicide, alcohol use disorder and depressive disorders should be prioritized through literacy and educational therapy programs. Adherence is a construct that can vary considerably from year to year in schizophrenia, and therefore may be amenable to interventions for its improvement. However, caution is also warranted as nearly one in five patients with initially good adherence experienced worsened adherence 1 year later.
Published: 2023
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5. Immuno-metabolic profile of patients with psychotic disorders and metabolic syndrome. Results from the FACE-SZ cohort

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

Author: Nora Hamdani, Djaouida Bengoufa, Ophélia Godin, Raphaël Doukhan, Emmanuel Le Guen, Claire Daban-Huard, Meriem Bennabi, Marine Delavest, Jean-Pierre Lépine, Wahid Boukouaci, Hakim Laouamri, Josselin Houenou, Stéphane Jamain, Jean-Romain Richard, Philippe Lecorvosier, Robert Yolken, Krishnamoorthy Rajagopal, Marion Leboyer, and Ryad Tamouza
Subjects: Humoral immunity, Immunoglobulins, Bipolar disorder, Schizophrenia, Toxoplasma gondii, Psychiatry, RC435-571
Abstract: Abstract Background Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection. Methods 334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ. Results Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls. Conclusions Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.
Published: 2018
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7. Early and very early‐onset schizophrenia compared with adult‐onset schizophrenia: French FACE‐SZ database

Author: Nathalie Coulon, Ophélia Godin, Ewa Bulzacka, Caroline Dubertret, Jasmina Mallet, Guillaume Fond, Lore Brunel, Méja Andrianarisoa, George Anderson, Isabelle Chereau, Hélène Denizot, Romain Rey, Jean‐Michel Dorey, Christophe Lançon, Catherine Faget, Paul Roux, Christine Passerieux, Julien Dubreucq, Sylvain Leignier, Delphine Capdevielle, Myrtille André, Bruno Aouizerate, David Misdrahi, Fabrice Berna, Pierre Vidailhet, Marion Leboyer, and Franck Schürhoff
Subjects: adult‐onset schizophrenia, duration of untreated psychosis, early‐onset schizophrenia, symptomatology, very early‐onset schizophrenia, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Objective To compare the clinical symptomatology in patients with Early‐Onset Schizophrenia (EOS, N = 176), especially the subgroup Very Early Onset Schizophrenia (VEOS) and Adult Onset Schizophrenia (AOS, N = 551). Method In a large French multicentric sample, 727 stable schizophrenia patients, classified by age at onset of the disorder, were assessed using standardized and extensive clinical and neuropsychological batteries: AOS with onset ≥ 18 years and EOS with onset
Published: 2020
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8. Factors associated with lamotrigine concentration/dose ratio in individuals with bipolar disorders

Author: Margot Chouchana, Clément Delage, Ophélia Godin, Jean- Eudes Fontan, Frank Bellivier, Sebastien Gard, Valérie Aubin, Raoul Belzeaux, Caroline Dubertret, Emmanuel Haffen, Marion Leboyer, Emilie Olie, Philippe Courtet, Mircea Polosan, Paul Roux, Ludovic Samalin, Raymund Schwan, Antoine Lefrere, Vanessa Bloch, and Bruno Etain
Subjects: Pharmacology, Psychiatry and Mental health, Neurology, Pharmacology (medical), Neurology (clinical), Biological Psychiatry
Published: 2023
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9. The cost of mental health: Where do we stand in France?

Author: Charles Laidi, Laeticia Blampain-Segar, Ophélia Godin, Anne de Danne, Marion Leboyer, and Isabelle Durand-Zaleski
Subjects: Pharmacology, Psychiatry and Mental health, Neurology, Pharmacology (medical), Neurology (clinical), Biological Psychiatry
Published: 2023
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10. Gender differences in psychosocial function and self-reported health status in late-diagnosed autistic adults: results from the FACE-ASD national cohort

Author: Julien, Dubreucq, Romain, Coutelle, Mohamed, Lajnef, Ophélia, Godin, Anouck, Amestoy, Paola, Atzori, Jean-Marc, Baleyte, Olivier, Bonnot, Manuel, Bouvard, Nathalie, Coulon, David, Da Fonseca, Caroline, Demily, Richard, Delorme, Marine, Fabrowski, Marion, Givaudan, Fanny, Gollier-Briant, Fabian, Guenolé, Elise, Humeau, Sylvain, Leignier, Florian, Lejuste, Charlotte, Levy, Juliette, Rabot, Carmen M, Schröder, Marie, Valette, Marion, Leboyer, and Mario, Speranza
Subjects: Psychiatry and Mental health, Applied Psychology
Abstract: Background While adult outcome in autism spectrum disorder (ASD) is generally measured using socially valued roles, it could also be understood in terms of aspects related to health status – an approach that could inform on potential gender differences. Methods We investigated gender differences in two aspects of outcome related to health-status, i.e. general functioning and self-perceived health status, and co-occurring health conditions in a large multi-center sample of autistic adults. Three hundred and eighty-three participants were consecutively recruited from the FondaMental Advanced Centers of Expertise for ASD cohort (a French network of seven expert centers) between 2013 and 2020. Evaluation included a medical interview, standardized scales for autism diagnosis, clinical and functional outcomes, self-perceived health status and verbal ability. Psychosocial function was measured using the Global Assessment of Functioning scale. Results While autistic women in this study were more likely than men to have socially valued roles, female gender was associated with poorer physical and mental health (e.g. a 7-fold risk for having three or more co-occurring physical health conditions) and a poorer self-perceived health status. Psychosocial function was negatively associated with depression and impairment in social communication. Half of the sample had multiple co-occurring health conditions but more than 70% reported that their visit at the Expert Center was their first contact with mental health services. Conclusions To improve objective and subjective aspects of health outcome, gender differences and a wide range of co-occurring health conditions should be taken into account when designing healthcare provision for autistic adults.
Published: 2022
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11. Current (but not ex) cigarette smoking is associated with worse cognitive performances in schizophrenia: results from the FACE-SZ cohort

Author: Jasmina, Mallet, Ophélia, Godin, Yecodji, Dansou, Nicolas, Mazer, Claire, Scognamiglio, Fabrice, Berna, Laurent, Boyer, Delphine, Capdevielle, Isabelle, Chéreau, Thierry, D'Amato, Julien, Dubreucq, Guillaume, Fond, Sylvain, Leigner, Pierre-Michel, Llorca, David, Misdrahi, Christine, Passerieux, Romain, Rey, Baptiste, Pignon, Mathieu, Urbach, Benoit, Schorr, Franck, Schürhoff, Le Strat, Yann, and Caroline, Dubertret
Subjects: Psychiatry and Mental health, Applied Psychology
Abstract: Background Tobacco use is common in subjects with schizophrenia (SZ) and has sometimes been associated with better functioning in short-term studies. Only few studies embrace an extensive examination of tobacco influence on clinical, cognitive and therapeutic characteristics in stabilized SZ outpatients. The objective of the present study was to assess the association between cognitive performances and smoking status in SZ subjects. Methods In total, 1233 SZ participants (73.9% men, mean age 31.5) were included and tested with a comprehensive battery. Tobacco status was self-declared (never-, ex-, or current smokers). Multivariable analyses including principal component analyses (PCA) were used. Results In total, 53.7% were smokers with 33.7% of them nicotine-dependent. Multiple factor analysis revealed that current tobacco smoking was associated with impaired general intellectual ability and abstract reasoning (aOR 0.60, 95% IC 0.41–0.88, p = 0.01) and with a lifetime alcohol use disorder (p = 0.026) and a lifetime cannabis use disorder (p < 0.001). Ex- and never-smokers differed for age, mean outcome, cannabis history and medication [ex-smokers being older (p = 0.047), likely to have higher income (p = 0.026), a lifetime cannabis use disorder (p < 0.001) and higher CPZeq doses (p = 0.005)]. Premorbid IQ in the three groups significantly differed with, from higher to lower: ex-smokers, never-smoker, current smokers (all p < 0.001). Conclusions This study is the largest to date providing strong evidence that chronic smoking is associated with cognitive impairment in SZ, arguing against the self-medication hypothesis as a contributor to the high prevalence of smoking in SZ. Ex-smokers may also represent a specific subgroup. Longitudinal studies are warranted to determine the developmental impact of tobacco on neurocognition.
Published: 2022

12. Pharmacological treatment profiles in the FACE-BD cohort: An unsupervised machine learning study, applied to a nationwide bipolar cohort✰

Author: Emilie Olié, Sébastien Brodeur, Chantal Henry, Jean-Luc Bosson, Paul Roux, Emmanuel Haffen, Bruno Aouizerate, Thierry Bougerol, Sébastien Gard, Hugo Terrisse, Frank Bellivier, Ludovic Samalin, Ophélia Godin, Raoul Belzeaux, Arnaud Pouchon, Caroline Dubertret, Raymund Schwan, Valerie Aubin, Bruno Etain, Marion Leboyer, Philippe Courtet, Mircea Polosan, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Louis Mourier - AP-HP [Colombes], Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Centre Hospitalier Universitaire [Grenoble] (CHU), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Bordeaux [Bordeaux], Centre Hospitalier Princesse Grace, Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Centre Hospitalier de Versailles André Mignot (CHV), CHU Clermont-Ferrand, and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: medicine.medical_specialty, Longitudinal study, Bipolar Disorder, Lithium (medication), [SDV]Life Sciences [q-bio], Disease, Lamotrigine, Pharmacological treatment, 03 medical and health sciences, 0302 clinical medicine, Antimanic Agents, Mood stabilizers, Internal medicine, medicine, Humans, Functioning, Longitudinal Studies, Bipolar disorder, ComputingMilieux_MISCELLANEOUS, Maintenance treatment, business.industry, Valproic Acid, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Mood, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, 030217 neurology & neurosurgery, Unsupervised Machine Learning, medicine.drug
Abstract: Background Despite thorough and validated clinical guidelines based on bipolar disorders subtypes, large pharmacological treatment heterogeneity remains in these patients. There is limited knowledge about the different treatment combinations used and their influence on patient outcomes. We attempted to determine profiles of patients based on their treatments and to understand the clinical characteristics associated with these treatment profiles. Methods This multicentre longitudinal study was performed on a French nationwide bipolar cohort database. We performed hierarchical agglomerative clustering to search for clusters of individuals based on their treatments during the first year following inclusion. We then compared patient clinical characteristics according to these clusters. Results Four groups were identified among the 1795 included patients: group 1 (“heterogeneous” n = 1099), group 2 (“lithium” n = 265), group 3 (“valproate” n = 268), and group 4 (“lamotrigine” n = 163). Proportion of bipolar 1 disorder, in groups 1 to 4 were: 48.2%, 57.0%, 48.9% and 32.5%. Groups 1 and 4 had greater functional impact at baseline and a less favorable clinical and functioning evolution at one-year follow-up, especially on GAF and FAST scales. Limitations The one-year period used for the analysis of mood stabilizing treatments remains short in the evolution of bipolar disorder. Conclusions Treatment profiles are associated with functional evolution of patients and were not clearly determined by bipolar subtypes. These profiles seem to group together common patient phenotypes. These findings do not seem to be influenced by the duration of disease prior to inclusion and neither by the number of treatments used during the follow-up period.
Published: 2021
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13. Direct medical cost of bipolar disorder: Insights from the FACE-BD longitudinal cohort

Author: Charles Laidi, Ophélia Godin, Bruno Etain, Frank Bellivier, Yannis Elandaloussi, Emilie Olié, Bruno Aouizerate, Sébastien Gard, Joséphine Loftus, Raoul Belzeaux, Caroline Dubertret, Hakim Laouamri, Christine Passerieux, Agnès Pelletier, Mircea Polosan, Raymund Schwan, Ludovic Samalin, Pierre-Michel Llorca, Philippe Courtet, Isabelle Durand-Zaleski, Marion Leboyer, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Fondation FondaMental [Créteil], Centre hospitalier Charles Perrens [Bordeaux], Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Princesse Grace, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Hôpital Louis Mourier - AP-HP [Colombes], Centre Hospitalier de Versailles André Mignot (CHV), Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Clermont-Ferrand, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Hôpital Hôtel-Dieu [Paris], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Authors express all our thanks to the nurses, and to the patients who were included in the present study. The authors thank Hakim Laouamri and his team (Seif Ben Salem, Karmène Souyris, Victor Barteau and Mohamed Laaidi) for the development of the FACE-BD computer interface (eBipolar©), data management, quality control and regulatory aspects., CHU Henri Mondor, Guerineau, Nathalie C., and Hôpital Charles Perrens
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, Bipolar disorder, Cost, Cost-Benefit Analysis, [SDV]Life Sciences [q-bio], Medico-economic, MESH: Health Care Costs, Health Care Costs, Cohort Studies, [SDV] Life Sciences [q-bio], Hospitalization, Psychiatry and Mental health, Clinical Psychology, MESH: Bipolar Disorder, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Cohort Studies, health care economics and organizations, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Cost-Benefit Analysis
Abstract: International audience; Background: Bipolar disorder (BD) is a severe chronic psychiatric disorder affecting 0.5 to 1% of the population worldwide. To date, most studies have estimated the cost of BD via information sourced from insurance claims with limited information on clinical characteristics and course of BD. The aims of this study are (i) to estimate the direct healthcare cost associated with BD and to identify contributing factors and (ii) to study the evolution of cost during a two-year follow-up period.Method: We analyzed a sample of 1116 individuals with BD included in the Advanced Centers of Expertise in Bipolar Disorder cohort. We estimated the direct healthcare cost per year and per patient, and we identified the clinical features of patients with BD associated with higher direct healthcare costs. In a subsample of patients followed up for two years centers of expertise for BD, we studied the evolution of direct healthcare cost.Results: The average cost of bipolar disorder was € 6910 per year and per patient. Clinical features of BD, sociodemographic characteristics, and associated addiction were associated with higher direct healthcare costs. In the subsample of patients followed-up for two years, direct healthcare cost dropped by more than 50%, strongly suggesting the beneficial effect of specialized care organization.Limitation: We did not estimate indirect healthcare and intangible costs.Conclusion: Our study investigates the cost of BD and its evolution in a deeply phenotyped longitudinal sample. Cost-utility and cost-effectiveness analyses are required to inform resource allocation decisions and to promote innovative healthcare organizations.
Published: 2022
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14. Association between childhood maltreatment and the clinical course of bipolar disorders: a survival analysis of mood recurrences

Author: Diane, Grillault Laroche, Ophélia, Godin, Raoul, Belzeaux, Katia, M'Bailara, Joséphine, Loftus, Philippe, Courtet, Caroline, Dubertret, Emmanuel, Haffen, Pierre Michel, Llorca, Emilie, Olie, Christine, Passerieux, Mircea, Polosan, Raymund, Schwan, Marion, Leboyer, Frank, Bellivier, Cynthia, Marie-Claire, Bruno, Etain, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Henri Mondor, Fondation FondaMental [Créteil], IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Charles Perrens [Bordeaux], Laboratoire de psychologie (LabPsy), Université de Bordeaux (UB), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Princesse Grace, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hôpital Louis Mourier - AP-HP [Colombes], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier de Versailles André Mignot (CHV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université de Lorraine (UL), 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, Université Paris Cité (UPCité), This research was supported by the Foundation FondaMental, Institut National de la Santé et de la Recherche Médicale (INSERM), AP- HP, and by the Investissements d’Avenir program managed by the ANR under reference ANR- 11- IDEX- 0004- 02 and ANR- 10-COHO- 10- 01. This work was supported by the Agence Nationale de la Recherche (ANR- 18-CE37- 0002). We thank INSERM and Labex BioPsy for the PhD funding (Poste Accueil) to DGL. CMC is supported by the Centre National pour la Recherche Scientifique (CNRS). These funding sources had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript for publication., FACE-BD collaborators, ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), ANR-18-CE37-0002,CT-ScarBip,MicroARNs et réseaux de gènes co-exprimés associés aux traumatismes dans l'enfance: de la cicatrice moléculaire aux pistes thérapeutiques dans les troubles bipolaires(2018), Hôpital Charles Perrens, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Guerineau, Nathalie C., Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, Cohortes - FondaMental-Cohortes - - Psy-COH2010 - ANR-10-COHO-0010 - COHO - VALID, and APPEL À PROJETS GÉNÉRIQUE 2018 - MicroARNs et réseaux de gènes co-exprimés associés aux traumatismes dans l'enfance: de la cicatrice moléculaire aux pistes thérapeutiques dans les troubles bipolaires - - CT-ScarBip2018 - ANR-18-CE37-0002 - AAPG2018 - VALID
Subjects: mood recurrence, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, childhood trauma, survival analyses, Bipolar disorder, [SDV]Life Sciences [q-bio], childhood maltreatment, Survival Analysis, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Recurrence, physical abuse, Surveys and Questionnaires, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Child Abuse, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Child, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Retrospective Studies
Abstract: International audience; Objectives: Childhood maltreatment, also referred as childhood trauma, increases the severity of Bipolar Disorders (BD). Childhood maltreatment has been associated with more frequent mood recurrences, however mostly in retrospective studies. Since scarce, further prospective studies are required to identify whether childhood maltreatment may be associated with the time to recurrence in BD.Methods: Individuals with BD (N=2008) were assessed clinically and for childhood maltreatment at baseline, and followed-up for two years. The cumulative probability of mood recurrence over time was estimated with the Turnbull's extension of the Kaplan-Meier analysis for interval-censored data, including childhood maltreatment as a whole, and then maltreatment subtypes as predictors. Analyses were adjusted for potential confounding factors.Results: The median duration of follow-up was 22.3 month (IQR:12.0-24.8). Univariable analyses showed associations between childhood maltreatment, in particular all types of abuses (emotional, physical and sexual) or emotional neglect, and a shorter time to recurrence (all p values
Published: 2022
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15. Association between mental disorders and COVID-19 outcomes among inpatients in France: A retrospective nationwide population-based study

Author: Alexandre Descamps, Jérôme Frenkiel, Kevin Zarca, Charles Laidi, Ophélia Godin, Odile Launay, Marion Leboyer, and Isabelle Durand-Zaleski
Subjects: Adult, Hospitalization, Psychiatry and Mental health, Inpatients, Mental Disorders, COVID-19, Humans, Dementia, Biological Psychiatry, Retrospective Studies
Abstract: Mental disorders are at-risk of severe COVID-19 outcomes. There is limited and heterogeneous national data in hospital settings evaluating the risks associated with any pre-existing mental disorder, and susceptible subgroups. Our study aimed to investigate the association between pre-existing psychiatric disorders and outcomes of adults hospitalised for COVID-19.We used data obtained from the French national hospital database linked to the state-level psychiatric registry. The primary outcome was 30-days in-hospital mortality. Secondary outcomes were to compare the length of hospital stay, Intensive Care Unit (ICU) admission and ICU length. Propensity score matching analysis was used to control for COVID-19 confounding factors between patients with or without mental disorder and stratified by psychiatric subgroups.Among 97 302 adults hospitalised for COVID-19 from March to September 2020, 10 083 (10.3%) had a pre-existing mental disorder, mainly dementia (3581 [35.5%]), mood disorders (1298 [12.9%]), anxiety disorders (995 [9.9%]), psychoactive substance use disorders (960 [9.5%]), and psychotic disorders (866 [8.6%]). In propensity-matched analysis, 30-days in-hospital mortality was increased among those with at least one pre-existing mental disorder (hazard ratio (HR) 1.15, 95% CI 1.08-1.23), psychotic disorder (1.90, 1.24-2.90), and psychoactive substance disorders (1.53, 1.10-2.14). The odds of ICU admission were consistently decreased for patients with any pre-existing mental disorder (OR 0.83, 95% CI 0.76-0.92) and for those with dementia (0.64, 0.53-0.76).Pre-existing mental disorders were independently associated with in-hospital mortality. These findings underscore the important need for adequate care and targeted interventions for at-risk individuals with severe mental illness.
Published: 2022

16. Recommendations of the treatment-resistant depression expert center network for promoting tobacco smoking cessation based on the results from the real-world FACE-TRD national cohort

Author: Alexandra Garosi, Christelle Andrieu-Haller, Olivier Doumy, Nicolas Suc, Julia Maruani, J.-B. Genty, Martin Breyton, Raphaëlle Richieri, Frank Bellivierid, Antoine Yrondid, Mathilde Horn, T Korchia, Guillaume Fond, Laurent Boyers, Rémi Moirand, Bruno Aouizerate, Jean Petrucci, Christophe Arbus, Michel Walter, Thierry Bougerol, Jérôme Holtzmann, Philippe Courtet, Vincent Camus, Christophe Lançon, Guillaume Vaiva, Pierre-Michel Llorca, Fanny Moliere, Djamila Bennabi, Wissam El-Hage, Florian Stephan, Mélanie Faugere, Ludovic Samalin, Romain Rey, Ophélia Godin, Marion Leboyer, Emmanuel Haffen, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Fondation FondaMental [Créteil], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Bourgogne Franche-Comté [COMUE] (UBFC), Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_treatment, MESH: Tobacco Smoking, Suicide, Attempted, tobacco, MESH: Nicotine, Cohort Studies, Depressive Disorder, Treatment-Resistant, chemistry.chemical_compound, Surveys and Questionnaires, Medicine, Precision Medicine, Varenicline, MESH: Cohort Studies, Depression (differential diagnoses), health care economics and organizations, education.field_of_study, public mental health, MESH: Middle Aged, MESH: Suicidal Ideation, public health, Middle Aged, MESH: Smoking Cessation, psychiatry, Cohort, depression, MESH: Suicide, Attempted, Female, mental health, Nicotine, medicine.medical_specialty, Population, education, MESH: Precision Medicine, smoking, Suicidal Ideation, MESH: Depressive Disorder, Treatment-Resistant, Sex Factors, MESH: Sex Factors, Tobacco Smoking, Humans, MESH: Surveys and Questionnaires, Psychiatry, Biological Psychiatry, Pharmacology, MESH: Humans, Suicide attempt, business.industry, Odds ratio, medicine.disease, MESH: Male, schizophrenia, chemistry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Smoking cessation, Smoking Cessation, business, Treatment-resistant depression, MESH: Female
Abstract: Background Tobacco smoking has been associated with suicide, impulsivity and depression in non-clinical populations with differences across sexes. Objective To determine the role of tobacco smoking in Treatment-Resistant Depression (TRD) according to sex in a precision-medicine approach. Method The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at 6 months. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at 6 months on their smoking and psychiatric hospitalization outcomes. Results 355 TRD participants were included (222 women). The smoking rate was much higher in TRD women compared to the French general population (34% vs 24%) while it was comparable for men (approximately 29%). In multivariate analyses, compared to non-smoking women, female smokers had significantly increased number of lifetime psychiatric hospitalizations (standardized beta B = 0.232, p = 0.014) and electro-convulsive therapy (adjusted odds ratio (aOR) = 2.748, p = 0.005), increased suicidal ideations (aOR = 4.047, p = 0.031), history of suicide attempt (aOR = 1.994, p = 0.033), and increased impulsivity (B = 0.210, p = 0.006) and were more frequently treated by benzodiazepines (aOR = 1.848, p = 0.035) and third- or fourth-line TRD treatments (antipsychotics aOR = 2.270, p = 0.006, mood stabilizers aOR = 2.067 p = 0.044). Tobacco smoking at baseline was predictive of psychiatric hospitalization within 6 months in persistent smoking women (aOR = 2.636, p = 0.031). These results were not replicated in men, for whom tobacco smoking was only associated with increased clinician-rated and self-reported depressive symptoms (respectively B = 0.207, p = 0.022 and B = 0.184, p = 0.048). The smoking cessation rate at 6 months was higher in women than in men (12% vs. 7%). No patient was administered nicotine substitute or varenicline at the two timepoints. Interpretation Combining these results and those of the literature, we recommend that active tobacco cessation should be promoted in TRD to improve depression, suicide and impulsivity especially in women. Female smokers appear as a specific population with heavier mental health outcomes that should be specifically addressed.
Published: 2022
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17. Precision-medicine findings from the FACE-SZ cohort to develop motivation-enhancing programs in real-world schizophrenia

Author: Théo Korchia, Maud Tastevin, Pierre-Louis Sunhary de Verville, Ridha Joober, Christelle Andrieu-Haller, Mélanie Faugere, Ophélia Godin, Damien Etchecopar-Etchart, Fabrice Berna, Bruno Aouizerate, Delphine Capdevielle, Isabelle Chereau, Julie Clauss-Kobayashi, Nathalie Coulon, Jean-Michel Dorey, Caroline Dubertret, Julien Dubreucq, Jasmina Mallet, David Misdrahi, Christine Passerieux, Romain Rey, Frank Schürhoff, Andrei Szoke, Mathieu Urbach, Marion Leboyer, Pierre-Michel Llorca, Christophe Lançon, Raphaelle Richieri, Laurent Boyer, Guillaume Fond, Fondation FondaMental [Créteil], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], 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, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Charles Perrens, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), 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), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPC), 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: Depressive Disorder, Major, Motivation, [SDV]Life Sciences [q-bio], mood disorders, psychiatry, schizophrenia, Psychiatry and Mental health, Alcoholism, quality of life, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Precision Medicine, depressive disorders, Biological Psychiatry, mental health, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: In people with schizophrenia, major areas of everyday life are impaired, including independent living, productive activities, social relationships and overall quality of life. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes.Aim: The goal of the present study was to identify factors associated with motivation deficits in real-life schizophrenia, and to assess its contribution to impaired functioning and quality of life.Methods: Based on previous literature and clinical experience, several factors were selected and grouped into factors potentially explaining motivation deficits. Some of these variables were never investigated before in relationship with motivation deficits.Results: In 561 patients with schizophrenia of the national FACE-SZ cohort living in the community, 235(41.9%) reported severe motivation deficits. These deficits were found to be significantly associated with impaired socially useful activities, psychological and physical quality of life (in almost all domains), alcohol use disorder (aOR =2.141, p = 0.021), severe nicotine dependence (aOR =2.906, p < 0.001) independently of age and sex. No significant association was found for body mass index, metabolic syndrome or physical activity level. In the second model, we identified the following modifiable factors associated with motivation deficits: history of suicide attempt (aOR =2.297, p = 0.001), positive symptoms (aOR =1.052, p = 0.006), current major depressive episode (aOR =2.627, p < 0.001), sleep disorders (aOR =1.474, p = 0.024) and lower medication adherence (aOR =0.836, p = 0.001) independently of gender, current alcohol use disorder, second-generation antipsychotics and akathisia. No significant association was found for negative symptoms, childhood trauma and inflammation. These results were maintained after removing patients with schizoaffective disorders or those with major depressive disorder.Interpretation: Motivation deficits are frequent and remain persistent unmet need in real-world schizophrenia that should be addressed in future guidelines. Based on our results, literature and clinical experience, we recommend to address in priority major depression, sleep, suicide, positive symptoms (when present and as early as possible) and medication adherence to improve motivation deficits of schizophrenia.
Published: 2022
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18. Redefining peripheral inflammation signature in schizophrenia based on the real-world FACE-SZ cohort

Author: Christophe Lançon, Baptiste Pignon, T Korchia, Guillaume Fond, Damien Etchecopar-Etchart, Raphaëlle Richieri, Christine Passerieux, Jasmina Mallet, David Misdrahi, Delphine Capdevielle, Mélanie Faugere, Mathieu Urbach, F. Schürhoff, N Coulon, Bruno Aouizerate, Romain Rey, Ophélia Godin, L. Boyer, Julien Dubreucq, P.L. Sunhary de Verville, Isabelle Chereau, Jean-Michel Dorey, Marion Leboyer, Julie Clauss-Kobayashi, Caroline Dubertret, Fabrice Berna, P.-M. Llorca, 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), Hôpital Henri Mondor, 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), Les Hôpitaux Universitaires de Strasbourg (HUS), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier Charles Perrens [Bordeaux], Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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), FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) Group: P M Llorca, C Lançon, L Boyer, Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), 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), 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-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Quality of life, medicine.medical_specialty, Inflammation, Overweight, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, Biological Psychiatry, Pharmacology, Psychiatry, business.industry, Patient Acuity, medicine.disease, Physical activity level, 3. Good health, 030227 psychiatry, Peripheral, C-Reactive Protein, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, Inflammatory biomarker, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers
Abstract: International audience; Background: Peripheral inflammation is associated with impaired prognosis in schizophrenia (SZ). Highly sensitive C-reactive protein (hs-CRP) is the most used inflammatory biomarker in daily practice. However, no consensual cut-off has been determined to date to discriminate patients with peripheral inflammation from those without.Aims: To determine if patients with peripheral inflammation between 1 and 3 mg/L had poorer outcomes compared to those with undetectable CRP ( 1 mg/L is a reliable marker to detect peripheral inflammation in patients with schizophrenia.
Published: 2021
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19. Handedness as a neurodevelopmental marker in schizophrenia: Results from the FACE-SZ cohort

Author: Jasmina, Mallet, Ophélia, Godin, Yann, Le Strat, Nicolas, Mazer, Fabrice, Berna, Laurent, Boyer, Delphine, Capdevielle, Julie, Clauss, Isabelle, Chéreau, Thierry, D'Amato, Julien, Dubreucq, Sylvain, Leigner, Pierre-Michel, Llorca, David, Misdrahi, Christine, Passerieux, Romain, Rey, Baptiste, Pignon, Mathieu, Urbach, Franck, Schürhoff, Guillaume, Fond, and Caroline, Dubertret
Subjects: Cohort Studies, Learning Disabilities, Schizophrenia, Humans, Functional Laterality, Psychomotor Agitation, Biomarkers
Abstract: High rates of non-right-handedness (NRH) including mixed-handedness have been reported in neurodevelopmental disorders. In schizophrenia (SZ), atypical handedness has been inconsistently related to impaired features. We aimed to determine whether SZ subjects with NRH and mixed-handedness had poorer clinical and cognitive outcomes compared to their counterparts.667 participants were tested with a battery of neuropsychological tests, and assessed for laterality using the Edinburg Handedness Inventory. Clinical symptomatology was assessed. Learning disorders and obstetrical complications were recorded. Biological parameters were explored.The prevalence of NRH and mixed-handedness was high (respectively, 42.4% and 34.1%). In the multivariable analyses, NRH was associated with cannabis use disorder (Non-right and mixed-handedness are very high in patients with SZ, possibly reflecting a neurodevelopmental origin. NRH is associated with learning disorders and cannabis use. Mixed-handedness is associated with positive symptoms, current depressive disorder, cannabis use and less akathisia. However, this study did not confirm greater cognitive impairment in these patients.
Published: 2021

20. Clinical characteristics of adults suffering from high-functioning autism and comorbid obsessive-compulsive disorder

Author: Hugues Lamothe, Ophélia Godin, Chloé Stengel, Safiyah Benmansour, Soline Burckard, Julie Brouillet Z, Jean Petrucci, Delphine Weil, Florian Lejuste, and Marion Leboyer
Subjects: Adult, Social Cognition, Psychiatry and Mental health, Obsessive-Compulsive Disorder, Autism Spectrum Disorder, Humans, Comorbidity, Autistic Disorder, Biological Psychiatry
Abstract: Autism spectrum disorder (ASD) is a very heterogeneous disorder. Obsessive compulsive disorder (OCD) comorbidity, frequent in ASD, could be useful to define a specific ASD subtype. Our objective was to explore if adults with ASD and comorbid OCD could present a specific clinical profile of ASD in 89 high functioning-adult ASD patients. We found that adults with ASD and comorbid OCD showed a lower verbal IQ and a more severe impairments in social cognition. ASD with comorbid OCD present a specific clinical profile which could constitute a possible subtype of ASD.
Published: 2021

21. Pharmacological treatment profiles in the FACE-BD cohort: Treatment description and complete data for bipolar subtypes

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

Author: Christine Passerieux, Raphaëlle Richieri, Romain Rey, Fabrice Berna, Isabelle Chereau, Ophélia Godin, Thierry d'Amato, P.-M. Llorca, Mathieu Urbach, Delphine Capdevielle, Caroline Dubertret, L. Boyer, Damien Etchecopar-Etchart, C. Lançon, Baptiste Pignon, Jasmina Mallet, Bruno Aouizerate, David Misdrahi, Sylvain Leignier, Marion Leboyer, Julien Dubreucq, P.L. Sunhary de Verville, Guillaume Fond, Pierre Vidailhet, F. Schürhoff, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut 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), Fondation FondaMental, Agence Nationale de la Recherche, ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), and ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010)
Subjects: Adult, Male, Sleep Wake Disorders, medicine.medical_specialty, Psychosis, Major depressive disorder, Akathisia, Cohort Studies, Pittsburgh Sleep Quality Index, 03 medical and health sciences, 0302 clinical medicine, PSQI, Surveys and Questionnaires, medicine, Brief Psychiatric Rating Scale, Humans, Mass Screening, Major depressive episode, Psychiatry, Expert Testimony, Biological Psychiatry, Migraine, 2. Zero hunger, Pharmacology, Depressive Disorder, Major, Positive and Negative Syndrome Scale, business.industry, Sleep disorders, medicine.disease, 030227 psychiatry, 3. Good health, FACE-SZ, Barnes Akathisia Scale, Sleep Quality, Psychotic Disorders, Schizophrenia, Female, Schizophrenic Psychology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business
Abstract: Background: Sleep disorders associated factors are under explored in schizophrenia while the literature suggests high and heterogeneous frequency. Aims: The objective of the present study was to determine the prevalence and risk factors of sleep disorders in the real-world FACE-SZ national cohort. Method: Stabilized schizophrenic outpatients were recruited in 10 expert centers for schizophrenia. Sleep quality was explored with the Pittsburgh Sleep Quality Index (PSQI) and sleep disorders was defined by a PSQI score > 5. Psychosis severity was measured with the Positive and Negative Syndrome Scale, current major depressive episode with the Calgary Depression Scale for Schizophrenia, verbal aggressiveness with the Buss-Perry Aggression Questionnaire, adherence to treatment with the Medication Adherence Rating Scale, akathisia with the Barnes Akathisia Scale. Current somatic comorbidities and body mass index were reported. Variables with P values
Published: 2021
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23. 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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24. Natural killer cells in first-episode psychosis: an innate immune signature?

Author: Ophélia Godin, Philippe Le Corvoisier, Caroline Barau, Wu Ching-Lien, Wahid Boukouaci, Patrice Debré, Djaouida Bengoufa, Jean Romain Richard, Nadine Tarantino, Katia Ledudal, Vincent Vieillard, Nora Hamdani, Marion Leboyer, Ryad Tamouza, Arthur Bouleau, Centre d'Immunologie et de Maladies Infectieuses (CIMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Psychosis, Bipolar Disorder, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Medicine, Cytotoxic T cell, Humans, Bipolar disorder, Receptor, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Innate immune system, business.industry, medicine.disease, Immunity, Innate, Killer Cells, Natural, Psychiatry and Mental health, 030104 developmental biology, Cytokine, Psychotic Disorders, Schizophrenia, Immunology, business, Cell activation, 030217 neurology & neurosurgery
Abstract: Accumulating evidence majorly implicates immune dysfunction in the etiology of psychotic disorders. In particular, altered numbers and functions of natural killer (NK) cells have been described in psychosis, but interpretation has often been confounded by a number of biases, including treatment. Eighty-one first-episode psychosis (FEP) patients who subsequently received a diagnosis of either schizophrenia (SZ; n = 30) or bipolar disorder (BP; n = 31) over a five-year follow-up period were investigated for their NK cell phenotype and compared to 61 healthy controls (HCs). We found a similar proportion of CD3-CD56+ NK cells in FEP patients and HCs. The frequency of NK cells expressing the late cell activation marker HLA-DR was significantly increased in FEP patients compared to HCs, especially in patients with BP (p < 0.0001) and, to a lesser degree, in patients with SZ (p = 0.0128). Interestingly, the expression of the activating NKG2C receptor, known to be associated with infections, was higher in patients with SZ and BP than in HCs (p < 0.0001) and correlated with HLA-DR expression, altogether defining adaptive NK cells. In terms of NK cell function, we observed a suppressed capacity of SZ-derived NK cells to mount cytotoxic responses in the presence of target cells, while NK cells from patients with BP show an inability to produce IFN-γ, a cytokine pivotal to NK function. This study strongly suggests major dysfunction of NK cells in FEP with functioning impairment correlated with psychotic, manic, and depressive symptoms in subsequently diagnosed patients with SZ and BP.
Published: 2021
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25. The course of bipolar disorder as a function of the presence and sequence of onset of comorbid alcohol use disorders in outpatients attending the Fondamental Advanced Centres of Expertise

Author: Sébastien Guillaume, Marion Leboyer, Frank Bellivier, Katia M'Bailara, Georges Brousse, Isabelle Biseul, Nicolas Mazer, Emilie Olié, Philippe Courtet, Raymund Schwan, Joséphine Loftus, Valentin Flaudias, Sébastien Gard, Paul Roux, Ludovic Samalin, Ophélia Godin, Romain Icick, Iréna Cussac, Pierre-Michel Llorca, Bruno Etain, Mircea Polosan, Chantal Henry, Emmanuel Haffen, Valerie Aubin, Raoul Belzeaux, Fondation FondaMental [Créteil], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier Charles Perrens [Bordeaux], CHU Clermont-Ferrand, Hôpital Princesse Grace [Monaco], Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Centre Psychothérapique de Nancy [Laxou] (CPN), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier de Versailles André Mignot (CHV), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Hôpital Louis Mourier - AP-HP [Colombes], Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoires de neurosciences intégratives et cliniques (EA 481), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), ANR-10-COHO-10-01 Institut National de la Santé et de la Recherche Médicale, Inserm Agence Nationale de la Recherche, ANR Assistance Publique - Hôpitaux de Paris, AP-HP, This research was supported by the Foundation FondaMental, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique des Hôpitaux de Paris (AP-HP), and by the Investissements d'Avenir program managed by the Agence National de la Recherche (ANR) under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. The funding sources had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript for publication., ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Charles Perrens, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Psychothérapique de Nancy (CPN), Hôpital Lapeyronie [Montpellier] (CHU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut de Génomique Fonctionnelle (IGF), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Bipolar Disorder, Alcohol use disorder, Comorbidity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, Outpatients, medicine, Prevalence, Humans, Dual diagnosis, Bipolar disorder, Clinical trajectory, Sequence of onset, Sequence (medicine), business.industry, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Alcoholism, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Binary regression, business, 030217 neurology & neurosurgery
Abstract: International audience; Objectives: The comorbidity of alcohol use disorder (AUD) and bipolar disorder (BD) has been repeatedly associated with poorer clinical outcomes than BD without AUD. We aimed to extend these findings by focusing on the characteristics associated with the sequence of onset of BD and AUD. Methods: 3,027 outpatients from the Fondamental Advanced Centres of Expertise were ascertained for BD-1, BD-2 and AUD diagnoses, including their respective ages at onset (AAOs, N =2,804). We selected the variables associated with both the presence and sequence of onset of comorbid AUD using bivariate analyses corrected for multiple testing to enter a binary regression model with the sequence of onset of BD and AUD as the dependent variable (AUD first - which also included 88 same-year onsets, vs. BD first). Results: BD patients with comorbid AUD showed more severe clinical profile than those without. Compared to BD-AUD (N =269), AUD-BD (N =276) was independently associated with a higher AAO of BD (OR =1.1, p
Published: 2020
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26. Metabolic syndrome and actigraphy measures of sleep and circadian rhythms in bipolar disorders during remission

Author: H Brochard, C. Boudebesse, Pierre A. Geoffroy, J. Maruani, Chloé Benizri, V Benard, Bruno Etain, Ophélia Godin, Marion Leboyer, Sunthavy Yeim, and Frank Bellivier
Subjects: Adult, Male, Sleep Wake Disorders, medicine.medical_specialty, Bipolar Disorder, Systole, Blood Pressure, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Bipolar disorder, Circadian rhythm, Triglycerides, Monitoring, Physiologic, Metabolic Syndrome, business.industry, Confounding, Sleep apnea, Actigraphy, Middle Aged, Atherosclerosis, medicine.disease, Sleep in non-human animals, Circadian Rhythm, 030227 psychiatry, Psychiatry and Mental health, Blood pressure, Cardiology, Female, France, Metabolic syndrome, Sleep, business, 030217 neurology & neurosurgery, Antipsychotic Agents
Abstract: Objective This study explored the correlations between sleep and circadian rhythm measures and the metabolic syndrome (MetS) components in remitted patients with bipolar disorder (BD). Method Euthymic patients with BD (n = 67) were recorded by 3 weeks with actigraphy. We used nonparametric correlations to study the links between the MetS parameters, atherogenic index of plasma (AIP), sleep efficacy, sleep latency, fragmentation index, and phase and amplitude of rhythms. We performed multivariable analyses to take into account potential confounding factors such as sleep apnea risk, antipsychotics use, and smoker status. Results We found correlations between lower sleep efficiency and higher triglyceride levels (P = 0.002), lower M10 onset (beginning of the 10 most active hours during the 24-h cycle) and higher systolic blood pressure (P = 0.03), higher fragmentation index and higher systolic blood pressure (P = 0.009), lower sleep efficiency, higher fragmentation index, and higher AIP (respectively P = 0.02 and P = 0.04). These correlations mostly remained significant when adjusting for confounders, with the exception of M10 onset and systolic blood pressure. Conclusion Sleep efficiency and fragmentation index might contribute to the cardiovascular risk of patients with BD independently of major confounding factors. Although these associations did not imply causality, proposing interventions on sleep quality and circadian rhythm regularity might contribute to reduce cardiovascular risk in patients with BD.
Published: 2018
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27. Major depression, sleep, hostility and body mass index are associated with impaired quality of life in schizophrenia. Results from the FACE-SZ cohort

Author: Baptiste Pignon, Myrtille André, L. Boyer, C. Lançon, Delphine Capdevielle, Caroline Dubertret, T Korchia, David Misdrahi, P.L. Sunhary de Verville, Sylvain Leignier, Fabrice Berna, Jasmina Mallet, Mathieu Urbach, Guillaume Fond, Thierry d'Amato, Pierre-Michel Llorca, Pierre Vidailhet, Christine Passerieux, F. Schürhoff, Bruno Aouizerate, Julien Dubreucq, Isabelle Chereau, Andrei Szöke, Romain Rey, Ophélia Godin, Marion Leboyer, Fondation FondaMental [Créteil], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), SECOP - centre hospitalier Charles Perrens, Université de Bordeaux (UB), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), epartment of Addictology, Ramsay- General de Santé, SSR Petit Colmoulins, Harfleur, France, University Hospital Cochin (site Tarnier), University Sorbonne Paris-Cité (Paris V), Faculty of Medicine Paris Descartes, INSERM U894, Centre Psychiatry and Neurosciences, Paris, France. Electronic address: sandrine.lamy74@gmail.com., Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Centre Hospitalier Charles PERRENS, 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), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANR-10-COHO-10-01 Assistance Publique - HÃ´pitaux de Paris, AP-HP Institut National de la SantÃ© et de la Recherche MÃ©dicale, Inserm, This work was funded by AP-HM (Assistance Publique des Hôpitaux de Marseille), 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)., ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), 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 de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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 Charles Perrens, Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre 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), and Centre hospitalier Charles Perrens [Bordeaux]
Subjects: Male, Global Assessment of Functioning, Hostility, Body Mass Index, Pittsburgh Sleep Quality Index, 03 medical and health sciences, 0302 clinical medicine, Quality of life, medicine, Major depression, Humans, Psychiatry, 2. Zero hunger, Depressive Disorder, Major, Positive and Negative Syndrome Scale, business.industry, Depression, Sleep quality, Weight, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Mood, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Quality of Life, Female, medicine.symptom, business, Sleep, Body mass index, 030217 neurology & neurosurgery, Clinical psychology
Abstract: International audience; Background: Impaired Quality of life (QoL) in schizophrenia has been mostly associated with psychotic and mood symptomatology, insight and functioning so far. Aims: QoL levels remain unsatisfactory due to other factors we aim to explore. Method: We have explored sleep quality with the Pittsburgh Sleep Quality Index, hostility with the Buss&Perry questionnaire, major depression with the Positive and Negative Syndrome Scale depressive factor, functioning with the Global Assessment of Functioning scale and weight gain with body mass index in addition to other classical QoL-associated factors. Results: 559 patients (mean age=31 (SD 9) years, 74% male sex) were included in the national FACE-SZ cohort. Impaired QoL has been significantly associated with respectively major depression, impaired sleep quality, increased hostility, impaired functioning and impaired insight independently of age, sex, treatments, tobacco smoking and body mass index. Major depression was associated with impaired psychological and physical well-being, and impaired self-esteem. Impaired sleep quality has been associated with impaired psychological and physical well-being and sentimental life. Hostility has been associated with impaired psychological well-being and self-esteem, impaired friends’ relationships and impaired autonomy. Weight was associated with impaired physical well-being. Tobacco smoking was associated with higher level of friends’ relationships. Conclusions: Major depression, sleep, hostility, and weight gain have been identified as potential targets to improve QoL in schizophrenia and should be implemented in the recommendations for good practice to optimize schizophrenia care.
Published: 2020
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28. Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort

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

Author: Romain Rey, Ophélia Godin, Pierre Vidailhet, Jasmina Mallet, Hélène Denizot, Christophe Lançon, Myrtille André, Isabelle Chereau, E. Bulzacka, Paul Roux, Marion Leboyer, Lore Brunel, Catherine Faget, N Coulon, David Misdrahi, George M. Anderson, Sylvain Leignier, Franck Schürhoff, Guillaume Fond, Fabrice Berna, Caroline Dubertret, Jean-Michel Dorey, Delphine Capdevielle, Christine Passerieux, Bruno Aouizerate, Julien Dubreucq, M. Andrianarisoa, Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation FondaMental [Créteil], Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), CRC Scotland & London, Service de psychiatrie, 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), Pôle de psychiatrie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-CHU Marseille, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), 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 (UGA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance Publique-Hôpitaux de Marseille (AP-HM), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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, Pediatrics, medicine.medical_specialty, Databases, Factual, Untreated psychosis, 050105 experimental psychology, early‐onset schizophrenia, lcsh:RC321-571, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, very early‐onset schizophrenia, medicine, Humans, 0501 psychology and cognitive sciences, In patient, Age of Onset, Child, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, Psychiatric Status Rating Scales, Early onset schizophrenia, business.industry, 05 social sciences, Neuropsychology, medicine.disease, Prognosis, Very early onset, 3. Good health, Psychotic Disorders, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, symptomatology, dup, Female, Schizophrenic Psychology, France, business, duration of untreated psychosis, 030217 neurology & neurosurgery, adult‐onset schizophrenia
Abstract: Objective To compare the clinical symptomatology in patients with Early‐Onset Schizophrenia (EOS, N = 176), especially the subgroup Very Early Onset Schizophrenia (VEOS) and Adult Onset Schizophrenia (AOS, N = 551). Method In a large French multicentric sample, 727 stable schizophrenia patients, classified by age at onset of the disorder, were assessed using standardized and extensive clinical and neuropsychological batteries: AOS with onset ≥ 18 years and EOS with onset, To describe schizophrenia from childhood to adulthood is complex and patients with early‐onset schizophrenia (EOS) remain undiagnosed or misclassified, especially the subgroup with very early‐onset schizophrenia (VEOS). In patients with VEOS, the DUP which exceeds 8 years, almost eight times higher than in patients with AOS, objective the problem of early diagnosis and the need to develop diagnostic programs and management cares.
Published: 2020
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30. Improving diet for psychiatric patients : High potential benefits and evidence for safety

Author: Guillaume Fond, Laurent Boyer, Allan H. Young, Pascal Auquier, Ophélia Godin, Christophe Lançon, Morgan Messiaen, Aix Marseille Université (AMU), Assistance Publique-Hôpitaux de Marseille (AP-HM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), King‘s College London, Université Pierre et Marie Curie - Paris 6 (UPMC), Pôle de psychiatrie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-CHU Marseille, and Assistance Publique - Hôpitaux de Marseille (APHM)
Subjects: medicine.medical_specialty, Mediterranean diet, High-protein diet, Disease, medicine.disease_cause, Diet, Mediterranean, 03 medical and health sciences, 0302 clinical medicine, Weight loss, Diabetes mellitus, Intermittent fasting, medicine, Humans, Psychiatry, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, business.industry, Mental Disorders, Fasting, medicine.disease, Mental health, 030227 psychiatry, 3. Good health, Diet, Psychiatry and Mental health, Clinical Psychology, Mental Health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, medicine.symptom, Diet, Healthy, business, 030217 neurology & neurosurgery
Abstract: Background Psychonutrition, i.e. the impact of diet on mental health, is an emerging field of psychiatry. Objective The purpose of the present letter was to highlight recent findings in the field to guide nutritional interventions in psychiatry. Method An overview of the most recent meta-analyses in the field of psychonutrition in severe mental disorders has been carried out. Results The Mediterranean diet showed the best evidence for effectiveness in diminishing the incidence of depressive symptomatology Complementary agents were found to be associated with lower depression levels (even in psychiatric populations): omegas 3 fatty acids, vitamin D, methylfolate and S-adenosylmethionine, all being found in high rates in the Mediterranean diet. The Healthy Eating Index (HEI) has also been found to be associated with lower depression. Moreover, major depression has been associated with inflammatory disturbances and a diet with a low Dietary Inflammatory Index has also been shown to be associated with lower depression. These effects may be mediated by microbiota modifications and probiotic supplementation has been recently shown to be effective in the treatment of depression. A high protein diet may also be particularly useful in psychiatry. The high protein diet has shown effectiveness in weight loss and increasing satiety with no evidence for deleterious effects in subjects without chronic conditions like renal failure, diabetes or cardiovascular disease. A reduction of 20% of calorific intake +/- intermittent fasting (i.e. fasting for 12 to 16 h per day) may also improve microbiota and therefore psychiatric conditions. Conclusion In light of these findings, diet modifications appear to be an underutilized tool with which to improve the mental and physical health of psychiatric patients.
Published: 2019
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31. P.117 Immunological profiling of psychotic patients with metabolic syndrome

Author: Susana Barbosa, Ophélia Godin, Nicolas Glaichenhaus, M. Foiselle, M. Leboyer, and Ryad Tamouza
Subjects: Pharmacology, Psychiatry and Mental health, Neurology, business.industry, Profiling (information science), Medicine, Pharmacology (medical), Neurology (clinical), Metabolic syndrome, Bioinformatics, business, medicine.disease, Biological Psychiatry
Published: 2021
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32. Predictors and Clinical Impact of Incident Lacunes in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Author: Martin Dichgans, Marco Duering, Hugues Chabriat, Eric Jouvent, François De Guio, Ophélia Godin, Yifeng Ling, and Dominique Hervé
Subjects: Adult, Male, medicine.medical_specialty, Perseveration, Trail Making Test, CADASIL, 030204 cardiovascular system & hematology, Logistic regression, Leukoencephalopathy, 03 medical and health sciences, 0302 clinical medicine, epidemiology [Stroke, Lacunar], Predictive Value of Tests, Modified Rankin Scale, Internal medicine, medicine, Humans, ddc:610, Prospective Studies, Risk factor, diagnostic imaging [Stroke, Lacunar], Stroke, Advanced and Specialized Nursing, business.industry, Incidence, epidemiology [CADASIL], Middle Aged, medicine.disease, Magnetic Resonance Imaging, diagnostic imaging [CADASIL], Stroke, Lacunar, Cardiology, Physical therapy, Female, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background and Purpose— Previous studies in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy showed that accumulation of lacunes strongly relate to clinical severity. However, the potential predictors of incident lacunes and their clinical consequences over a short time frame have not been investigated. This study aimed to determine the predictors and clinical impact of such lesions in a large cohort of patients. Methods— Two hundred and six NOTCH3 mutation carriers (mean age, 49.5±10.6 years) were followed up over 3 years. Incident lacunes were identified using difference imaging from 3-dimensional T1 images. Clinical events and change in different clinical scores such as the Mattis Dementia Rating Scale, Modified Rankin Scale, Barthel index, and time to complete part A and part B of Trail Making Test were recorded. Associations were analyzed with multivariable logistic regression analysis and ANCOVA. Results— Over a mean period of 3.4±0.7 years, incident lacunes occurred in 51 of 206 patients. Both the number of lacunes ( P P 140 mm Hg. Incident lacunes were also associated with incident stroke and with change in time to complete Trail Making Test part B, initiation/perseveration subscale of the Mattis Dementia Rating Scale and Barthel Index over the study period. Conclusions— Systolic blood pressure and the number of prevalent lacunes are independent predictors of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These lesions mainly impact executive performances and functional independence over 3 years.
Published: 2017
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33. Effects of Cumulative Herpesviridae and Toxoplasma gondii Infections on Cognitive Function in Healthy, Bipolar, and Schizophrenia Subjects

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

Author: C. Boudebesse, Chantal Henry, Bruno Etain, H Brochard, Marion Leboyer, and Ophélia Godin
Subjects: 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Arts and Humanities (miscellaneous), 030217 neurology & neurosurgery, 030227 psychiatry
Abstract: De nombreuses etudes montrent que la prevalence du syndrome metabolique est plus elevee chez les patients bipolaires que dans la population generale. En effet, entre 36 et 49 % de ces patients presentent des troubles metaboliques (Vancampfort, 2013), ce qui aggrave leur pronostic. La presence de troubles metaboliques chez ces patients peut etre expliquee par de nombreux facteurs comme une hygiene de vie a risque, une vulnerabilite genetique, la frequence des episodes depressifs ou les comorbidites psychiatriques, et les traitements psychotropes. D’autre part, ces patients presentent des perturbations de leurs rythmes circadiens, meme lors des periodes normothymiques. Plusieurs etudes recentes ont montre une correlation entre des perturbations circadiennes et des marqueurs metaboliques chez des patients bipolaires. L’objectif de cette revue est de mettre en evidence un lien possible entre troubles circadiens et du sommeil et anomalies metaboliques chez les patients bipolaires, et les voies physiopathologiques possiblement impliquees. Dans la population generale, des voies de regulation ont ete mises en evidence pour expliquer de tels liens, via des hormones comme la leptine et la ghreline. Une de nos hypotheses est l’implication de ces voies dans la vulnerabilite des patients bipolaires aux troubles metaboliques. Cette hypothese est appuyee par des donnees de la litterature recente sur des perturbations de ces hormones dans des maladies psychiatriques dont le trouble bipolaire. D’autres mecanismes semblent egalement en jeu, impliquant une deregulation de la secretion de melatonine et des mecanismes inflammatoires [Resume d'auteur]
Published: 2016
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35. Prevalence and characteristics of migraine in CADASIL

Author: Eric Jouvent, Hugues Chabriat, Nassira Alili, Stéphanie Guey, Marco Duering, Jérôme Mawet, Martin Dichgans, Ophélia Godin, Christian Opherk, and Dominique Hervé
Subjects: Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Aura, Migraine with Aura, CADASIL, Comorbidity, Cohort Studies, Leukoencephalopathy, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, Atrophy, Risk Factors, Germany, Prevalence, medicine, Humans, Sex Distribution, Psychiatry, Prospective cohort study, Aged, business.industry, General Medicine, Middle Aged, medicine.disease, Migraine with aura, 030104 developmental biology, Migraine, Cortical spreading depression, Female, France, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Background and objective Migraine with aura (MA) is a major symptom of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We assessed the spectrum of migraine symptoms and their potential correlates in a large prospective cohort of CADASIL individuals. Methods A standardized questionnaire was used in 378 CADASIL patients for assessing headache symptoms, trigger factors, age at first attack, frequency of attacks and associated symptoms. MRI lesions and brain atrophy were quantified. Results A total of 54.5% of individuals had a history of migraine, mostly MA in 84% of them; 62.4% of individuals with MA were women and age at onset of MA was lower in women than in men. Atypical aura symptoms were experienced by 59.3% of individuals with MA, and for 19.7% of patients with MA the aura was never accompanied by headache. MA was the inaugural manifestation in 41% of symptomatic patients and an isolated symptom in 12.1% of individuals. Slightly higher MMSE and MDRS scores and lower Rankin score were detected in the MA group. Conclusion MA is observed in almost half of all CADASIL patients. Atypical aura symptoms are reported by more than one in two of them. MA is often inaugural, can remain isolated and is not associated with the severity of the disorder.
Published: 2016
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36. Sexual dysfunctions are associated with major depression, chronic inflammation and anticholinergic consumption in the real-world schizophrenia FACE-SZ national cohort

Author: C. Passerieux, Catherine Faget, Jasmina Mallet, Mathieu Urbach, Pierre Vidailhet, F. Schürhoff, Isabelle Chereau, Caroline Dubertret, Bruno Aouizerate, C. Lançon, Pierre-Michel Llorca, Delphine Capdevielle, Marion Dumontaud, Julien Dubreucq, David Misdrahi, A. Schandrin, Guillaume Fond, Sylvain Leignier, Marion Leboyer, Andrei Szöke, Romain Rey, Ophélia Godin, Fabrice Berna, L. Boyer, and Thierry d'Amato
Subjects: Olanzapine, Adult, Male, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Comorbidity, Cholinergic Antagonists, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Anticholinergic, Humans, Sexual Dysfunctions, Psychological, Medical prescription, Antipsychotic, Biological Psychiatry, Depression (differential diagnoses), Pharmacology, Inflammation, Depressive Disorder, Major, business.industry, medicine.disease, 030227 psychiatry, 3. Good health, Schizophrenia, Case-Control Studies, Cohort, Chronic Disease, Major depressive disorder, Female, France, business, 030217 neurology & neurosurgery, medicine.drug, Antipsychotic Agents
Abstract: Background Sexual dysfunctions (SD) are frequent in schizophrenia (SZ) and associated with treatment withdrawal, however they remain under-explored and under-treated. To date, most of the studies have focused on SD as antipsychotics' side effects in therapeutic trials. Aims The objectives of the present study were to determine the SD prevalence in stabilized SZ outpatients and their clinical, pharmacological and biological correlates. Method Two hundred and thirty-seven participants (61.2% men) were consecutively included and received a thorough 2 days- clinical assessment including the self-reported Sexual Functioning Questionnaire (SFQ). SD was defined by a SFQ score ≥ 8. Results Two hundred and thirty-seven subjects were recruited in the FACE-SZ cohort, 41% of them reported sexual dysfunctions. In multivariate analyses, SD have been associated with current major depressive disorder (adjusted odd ratio aOR = 2.29[1.08–4.85], p = .03), anticholinergic prescription (aOR = 2.65, p = .02) and chronic low-grade inflammation (aOR = 2.09, p = .03) independently of age, gender, current cannabis use disorder and olanzapine prescription. No antipsychotic has been associated with increased or decreased SD rate. Conclusions SD are frequent in SZ subjects. Major depression, anticholinergic prescription and chronic low-grade peripheral inflammation may be the three targets of interest for addressing this specific issue.
Published: 2019

37. Inflammatory DEpression Advances in Schizophrenia (IDEAS): A precision medicine approach of the national FACE-SZ cohort

Author: David Misdrahi, Sylvain Leignier, Isabelle Chereau, Mathieu Urbach, Marion Leboyer, Pierre Vidailhet, C. Lançon, F. Schürhoff, Romain Rey, Ophélia Godin, L. Marulaz, Thierry d'Amato, Bruno Aouizerate, Caroline Dubertret, Jasmina Mallet, Catherine Faget, Julien Dubreucq, A. Schandrin, Pierre-Michel Llorca, C. Passerieux, Delphine Capdevielle, L. Boyer, Fabrice Berna, Guillaume Fond, Fondation FondaMental [Créteil], 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], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Departement de Psychiatrie, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), and Aix Marseille Université (AMU)
Subjects: Adult, Male, medicine.medical_specialty, Biological correlates, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Prevalence, Humans, Precision Medicine, Depression (differential diagnoses), Adiposity, Inflammation, Depressive Disorder, Major, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, Depression, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Cognition, Middle Aged, medicine.disease, Precision medicine, Antidepressive Agents, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Treatment Outcome, Schizophrenia, Cohort, Major depressive disorder, Antidepressant, Female, Schizophrenic Psychology, business, Toxoplasma, 030217 neurology & neurosurgery
Abstract: International audience; Background Major Depressive Disorder (MDD) is a therapeutic challenge in schizophrenia (SZ). Untangling different forms of MDD appears as the best current strategy to improve remission to treatment in the so-called precision medicine approach. Aims The objectives of the present study were to determine (i) the prevalence of Inflammatory Depression (ID) in stabilized SZ outpatients (ii) if ID was associated with clinical or cognitive profiles that may help clinicians detecting ID (iii) if antidepressants were effective in ID and (iv) the biological correlates of ID that may orientate personalized treatments.. Method Participants were consecutively included and received a thorough 2 days- clinical assessment. Results 785 subjects were recruited in the FACE-SZ cohort. 289 (36.8%) were diagnosed with MDD (remitted or unremitted), of them 57 with ID (19.7%). No clinical or cognitive features were associated with ID (all p > 0.05). ID has been associated with increased abdominal perimeter (aOR = 4.48, p = 0.002) and latent Toxoplasma infection (aOR = 2.19, p = 0.04). While antidepressants were associated with decreased depressive symptoms level in ID, 44% of the subjects remained unremitted under antidepressant, with no association with CRP blood levels. Conclusions ID may not differ from other forms of depression by its clinical symptoms but by its aetiologies. ID is associated with increased perivisceral fat and latent Toxoplasma infection that are both potentially related to gut/microbiota disturbances. Specific anti-inflammatory drugs and microbiota-targeted therapeutics appear as promising strategies in the treatment of inflammatory depression in schizophrenia.
Published: 2019
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38. Prevalence of Metabolic Syndrome and Associated Factors in a Cohort of Individuals With Treatment-Resistant Depression: Results From the FACE-DR Study

Author: Ophélia, Godin, Djamila, Bennabi, Antoine, Yrondi, Raphaelle, Richieri, Thierry, D'Amato, Franck, Bellivier, Thierry, Bougerol, Mathilde, Horn, Vincent, Camus, Philippe, Courtet, Olivier, Doumy, Jean Baptiste, Genty, Wissam, El-Hage, Frederic, Haesebaert, Jerôme, Holtzmann, Christophe, Lancon, Marion, Leboyer, Pierre Michel, Llorca, Julia, Maruani, Fanny, Molière, Ludovic, Samalin, Laurent, Schmitt, Florian, Stephan, Guillaume, Vaiva, Michel Walter Bruno, Aouizerate, and Emmanuel, Haffen
Subjects: Adult, Male, medicine.medical_specialty, Population, Comorbidity, Cohort Studies, 03 medical and health sciences, Depressive Disorder, Treatment-Resistant, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Prevalence, Humans, education, Major depressive episode, Depression (differential diagnoses), Metabolic Syndrome, education.field_of_study, Depressive Disorder, Major, business.industry, Middle Aged, medicine.disease, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Cohort, Female, France, medicine.symptom, business, Treatment-resistant depression, 030217 neurology & neurosurgery, Dyslipidemia, Cohort study
Abstract: BACKGROUND: The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) and its components in a cohort of French patients with treatment-resistant depression (TRD) and to determine correlations with sociodemographic, clinical, and treatment-related factors. METHODS: From 2012 to 2018, 205 patients who met DSM-IV criteria for major depressive episode with moderate-to-severe symptoms (Montgomery-Asberg Depression Rating Scale score ≥ 20), and at least Stage II resistance according to Thase and Rush criteria were enrolled in the FondaMental Advanced Centers of Expertise in Resistant Depression (FACE-DR) cohort. Data on sociodemographic and clinical characteristics, lifestyle information, and treatment and comorbidities were collected, and a blood sample was drawn. MetS was defined according to the criteria of the International Diabetes Federation. RESULTS: Overall, 38% of individuals with TRD met criteria for MetS. The frequency of MetS was significantly higher in men than in women only for patients aged 40 years or older (46.3% vs 35.2%, P = .0427). Moreover, whereas the management for diabetes was good, less than one-third of the patients with high blood pressure or dyslipidemia were treated for these conditions. Multivariate analysis showed that individuals with abnormal plasma c-reactive protein levels had a 3-fold increased risk (95% CI, 1.5-5.2) of having MetS, independent of other potential confounders. CONCLUSION: The prevalence of MetS is higher in patients with TRD than in those with other psychiatric disorders and characterized by a considerable undertreatment of some components of MetS in this population. Diagnosis and treatment of the components of MetS should be systematically performed to prevent the occurrence of cardiovascular diseases in patients with TRD. These findings highlight the need for integrated care, with more interaction and coordination between psychiatrists and primary care providers.
Published: 2019

39. Prevalence of and Risk Factors for Extrapyramidal Side Effects of Antipsychotics

Author: Thierry d'Amato, Guillaume Fond, Arnaud Tessier, Christophe Lançon, Romain Rey, Ophélia Godin, Wassilios G. Meissner, C. Passerieux, Mathieu Urbach, Jasmina Mallet, Franck Schürhoff, M. Andrianarisoa, Bruno Aouizerate, Laurent Boyer, Pierre-Michel Llorca, A. Schandrin, Delphine Capdevielle, Julien Dubreucq, Caroline Dubertret, Isabelle Chéreau-Boudet, Pierre Vidailhet, David Misdrahi, E. Bulzacka, Catherine Faget-Agius, Fabrice Berna, and Antoine Daubigney
Subjects: Adult, Male, Dyskinesia, Drug-Induced, medicine.medical_specialty, Medication Therapy Management, medicine.drug_class, medicine.medical_treatment, Tardive dyskinesia, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Risk Factors, law, Internal medicine, Prevalence, medicine, Anticholinergic, Humans, Tardive Dyskinesia, Parkinson Disease, Secondary, Antipsychotic, Psychiatric Status Rating Scales, Positive and Negative Syndrome Scale, business.industry, Odds ratio, medicine.disease, 030227 psychiatry, 3. Good health, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Dyskinesia, Schizophrenia, Female, France, Independent Living, medicine.symptom, business, Needs Assessment, 030217 neurology & neurosurgery, Antipsychotic Agents
Abstract: Background: Extrapyramidal side effects (EPS) have been identified as a complication of antipsychotic treatment. Previous meta-analyses have investigated EPS prevalence and risk factors in randomized clinical trials with highly selected patients, but studies in real-world schizophrenia are missing. Objective: To examine the prevalence and clinical correlates associated with EPS in a nonselected national multicenter sample of stabilized patients with schizophrenia. Methods: Between 2010 and 2016, patients suffering from schizophrenia (DSM-IV-TR criteria) were recruited through the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) network and data were collected during a comprehensive 1-day-long standardized evaluation. The Simpson-Angus Scale and the Abnormal Involuntary Movement Scale were used to assess drug-induced parkinsonism (DIP) and tardive dyskinesia, respectively. Results: The overall prevalence of DIP and tardive dyskinesia was 13.2% and 8.3%, respectively, in this community-dwelling sample of 674 patients. DIP was associated with negative symptoms (Positive and Negative Syndrome Scale [PANSS] subscore) (adjusted odds ratio [aOR] = 1.102, P < .001), first-generation antipsychotic prescription (aOR = 2.038, P = .047), and anticholinergic drug administration (aOR = 2.103, P = .017) independently of sex, age, disorganization (PANSS disorganized factor), and antipsychotic polytherapy. Tardive dyskinesia was associated with PANSS disorganized factor (aOR = 1.103, P = .049) independently of sex, age, negative symptoms, excitation, first-generation antipsychotic prescription, and benzodiazepine and anticholinergic drug administration. Conclusions: Our results indicate the high prevalence of EPS in a nonselected community-dwelling clinically stable sample of outpatients with schizophrenia. In the monitoring of antipsychotic treatment, EPS should be systematically evaluated, especially when negative symptoms and disorganization or cognitive alteration are present. Monotherapy with a second-generation antipsychotic should be preferentially initiated for patients with these side effects.
Published: 2019
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40. Brief Report: Impact of ART Classes on the Increasing Risk of Cerebral Small-Vessel Disease in Middle-Aged, Well-Controlled, cART-Treated, HIV-Infected Individuals

Author: Pierre-Marie Girard, Antoine Moulignier, Ophélia Godin, Christine Katlama, Laurence Salomon, Edouard Januel, François-Xavier Lescure, Dominique Costagliola, Julien Savatovsky, Nadia Valin, Gilles Pialoux, Roland Tubiana, Yazdan Yazdanpanah, Ana Canestri, Jean-Claude Sadik, Lambert Assoumou, Pascal Roux, Cédric Lamirel, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [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), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service des maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service des Maladies Infectieuses et Tropicales [CHU Tenon], and CHU Tenon [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], CD4-CD8 Ratio, Integrase inhibitor, Cumulative Exposure, HIV Infections, Disease, 030312 virology, 03 medical and health sciences, Pharmacotherapy, Leukoencephalopathies, Internal medicine, medicine, Dementia, Humans, Pharmacology (medical), Aged, 0303 health sciences, business.industry, Case-control study, Middle Aged, Viral Load, medicine.disease, 3. Good health, Infectious Diseases, Anti-Retroviral Agents, Case-Control Studies, Cerebral Small Vessel Diseases, Etiology, Regression Analysis, Drug Therapy, Combination, Female, business, Viral load, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral drug class could be associated with an increasing risk of CSVD.Methods: The MicroBREAK-2 case-control study (NCT02210130) enrolled PLHIVs aged 50 years and older, treated with combined antiretroviral therapy for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex, and year of HIV diagnosis (±5 years). Multivariable conditional logistic regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV transmission group.Results: Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs' median age was 57.6 years, and median HIV diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class.Conclusion: No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.
Published: 2019
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41. 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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42. Towards an improved access to psychiatric rehabilitation: availability and effectiveness at 1-year follow-up of psychoeducation, cognitive remediation therapy, cognitive behaviour therapy and social skills training in the FondaMental Advanced Centers of Expertise-Schizophrenia (FACE-SZ) national cohort

Author: Bruno Aouizerate, Julien Dubreucq, David Misdrahi, Thierry d'Amato, E. Giraud-Baro, Delphine Capdevielle, Romain Rey, E. Bulzacka, Ophélia Godin, M. Andrianarisoa, Guillaume Fond, L. Boyer, Lore Brunel, Mathieu Urbach, Agnès Hamon, Bernard Ycart, Raphaëlle Richieri, Fabrice Berna, Caroline Dubertret, Christine Passerieux, F. Gabayet, Jasmina Mallet, A. Schandrin, Pierre-Michel Llorca, Claire-Cécile Perier, Pierre Vidailhet, F. Schürhoff, Isabelle Chereau, Catherine Faget, Fondation FondaMental [Créteil], Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Statistique pour le Vivant et l’Homme (SVH), Laboratoire Jean Kuntzmann (LJK ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Sommeil, Addiction et Neuropsychiatrie [Bordeaux] (SANPSY), Université de Bordeaux (UB)-CHU de Bordeaux Pellegrin [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Institut Européen des membranes (IEM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Université Paris Diderot - Paris 7 (UPD7), Assistance Publique - Hôpitaux de Marseille (APHM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Departement de Psychiatrie, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Université de Strasbourg (UNISTRA), Réseau Handicap Psychique RéHPSY, ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-10-COHO-0010,Psy-COH,FondaMental-Cohortes(2010), Sommeil, Attention et Neuropsychiatrie [Bordeaux] (SANPSY), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM), and Assistance Publique-Hôpitaux de Marseille (AP-HM)
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, education.educational_degree, Psychological intervention, Psychiatric rehabilitation, Effectiveness, Health Services Accessibility, law.invention, Social Skills, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Quality of life, Randomized controlled trial, Patient Education as Topic, law, Outpatients, Psychoeducation, Medicine, Humans, Pharmacology (medical), Functioning, education, Biological Psychiatry, Cognitive Behavioral Therapy, business.industry, Rehabilitation, General Medicine, Middle Aged, Cognitive Remediation, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Cognitive remediation therapy, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Physical therapy, Quality of Life, Schizophrenia, Female, Schizophrenic Psychology, business, Psychosocial interventions, Psychosocial, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: International audience; Psychosocial Interventions (PIs) have shown positive effects on clinical and functional outcomes of schizophrenia (SZ) in randomized controlled trials. However their effectiveness and accessibility remain unclear to date in “real world” schizophrenia. The objectives of the present study were (i) to assess the proportion of SZ outpatients who benefited from PIs between 2010 and 2015 in France after an Expert Center Intervention in a national multicentric non-selected community-dwelling sample; (ii) to assess PIs’ effectiveness at 1-year follow-up. 183 SZ outpatients were recruited from FondaMental Advanced Centers of Expertise for Schizophrenia cohort. Baseline and 1-year evaluations included sociodemographic data, current treatments, illness characteristics and standardized scales for clinical severity, adherence to treatment, quality of life, a large cognitive battery, and daily functioning assessment. Only 7 (3.8%) received a PI before the evaluation, and 64 (35%) have received at least one PI during the 1-year follow-up. Having had at least one PI during the follow-up has been associated in multivariate analyses with significantly higher improvement in positive and negative symptoms (respectively p =0.031; p = 0.011), mental flexibility (TMT B, p = 0.029; C-VF, p = 0.02) and global functioning (p =0.042). CBT and SST were associated with higher cognitive improvements, while CRT was associated with clinical improvement. These results have not been demonstrated before and suggest that the effect of each PI is larger than its initial target. The present study has confirmed the PIs’ effectiveness in a large sample of community-dwelling SZ outpatients at 1 year follow-up. Efforts to improve access to PI should be reinforced in public health policies.
Published: 2018
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43. Machine learning for predicting psychotic relapse at 2 years in schizophrenia in the national FACE-SZ cohort

Author: A. Schandrin, E. Bulzacka, Guillaume Fond, Pierre Vidailhet, Delphine Capdevielle, Fabrice Berna, Mohamed Boucekine, Isabelle Chereau, Franck Schürhoff, Caroline Dubertret, L. Boyer, Romain Rey, Ophélia Godin, Thierry d'Amato, Pierre-Michel Llorca, Christine Passerieux, Jasmina Mallet, Bruno Aouizerate, Julien Dubreucq, Mathieu Urbach, C. Lançon, David Misdrahi, Sylvain Leignier, Catherine Faget, Marion Leboyer, 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), 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], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Departement de Psychiatrie, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), and Aix Marseille Université (AMU)
Subjects: Adult, Male, Low education, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, media_common.quotation_subject, Illness duration, Anger, Machine learning, computer.software_genre, Sensitivity and Specificity, Cohort Studies, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Recurrence, medicine, Early warning signs, Humans, Diagnosis, Computer-Assisted, Biological Psychiatry, media_common, Pharmacology, Psychiatric Status Rating Scales, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, medicine.disease, Prognosis, 030227 psychiatry, 3. Good health, Aggression, Psychotic Disorders, Schizophrenia, Cohort, Acute Psychotic Episode, Female, Schizophrenic Psychology, Cognitive Assessment System, Artificial intelligence, business, computer, Follow-Up Studies
Abstract: International audience; Background Predicting psychotic relapse is one of the major challenges in the daily care of schizophrenia. Objectives To determine the predictors of psychotic relapse and follow-up withdrawal in a non-selected national sample of stabilized community-dwelling SZ subjects with a machine learning approach. Methods Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical and cognitive assessment, including recording of current treatment. Relapse was defined by at least one acute psychotic episode of at least 7 days, reported by the patient, her/his relatives or by the treating psychiatrist, within the 2-year follow-up. A classification and regression tree (CART) was used to construct a predictive decision tree of relapse and follow-up withdrawal. Results Overall, 549 patients were evaluated in the expert centers at baseline and 315 (57.4%) (mean age = 32.6 years, 24% female gender) were followed-up at 2 years. On the 315 patients who received a visit at 2 years, 125(39.7%) patients had experienced psychotic relapse at least once within the 2 years of follow-up. High anger (Buss&Perry subscore), high physical aggressiveness (Buss&Perry scale subscore), high lifetime number of hospitalization in psychiatry, low education level, and high positive symptomatology at baseline (PANSS positive subscore) were found to be the best predictors of relapse at 2 years, with a percentage of correct prediction of 63.8%, sensitivity 71.0% and specificity 44.8%. High PANSS excited score, illness duration Conclusion Machine learning can help constructing predictive score. In the present sample, aggressiveness appears to be a good early warning sign of psychotic relapse and follow-up withdrawal and should be systematically assessed in SZ subjects. The other above-mentioned clinical variables may help clinicians to improve the prediction of psychotic relapse at 2 years.
Published: 2018
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44. Predictors of clinical or cerebral lesion progression in adult moyamoya angiopathy

Author: Hugues Chabriat, Christina Rogan, Lionel Calviere, Dominique Hervé, Marc-Antoine Labeyrie, Marie-Odile Habert, Sylvie Chevret, Elisabeth Tournier Lasserve, Nathanaelle Ibos-Augé, Jean Guichard, Ophélia Godin, and Manoelle Kossorotoff
Subjects: Adult, Male, medicine.medical_specialty, Clinical Decision-Making, Hemodynamics, Black People, Cerebral Revascularization, 030204 cardiovascular system & hematology, Risk Assessment, White People, Article, Angiopathy, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Asian People, Internal medicine, Medicine, Humans, Young adult, Cerebral perfusion pressure, Mortality, Stroke, Revascularization surgery, business.industry, medicine.disease, Prognosis, Ischemic Attack, Transient, Cerebrovascular Circulation, Cardiology, Disease Progression, Female, Neurology (clinical), France, Moyamoya Disease, business, Risk assessment, Intracranial Hemorrhages, 030217 neurology & neurosurgery
Abstract: ObjectiveTo identify independent predictors of clinical or cerebral lesion progression in a large sample of adult patients with moyamoya angiopathy (MMA) prior to decisions regarding revascularization surgery.MethodsNinety participants (median age, 37.5 years) were assessed at baseline and followed for a median time of 42.8 months. Incident ischemic and hemorrhagic strokes, death, as well as any incident ischemic and hemorrhagic lesions on MRI were recorded. Multiple demographic, clinical, and cerebral imaging measures at baseline were considered as potential predictors of clinical or cerebral tissue change at follow-up. Data were analyzed based on the Andersen-Gill counting process model, followed by internal validation of the prediction model.ResultsAmong multiple potential predictive measures considered in the analysis, Asian origin, a history of TIAs, and a reduction in hemodynamic reserve, as detected by imaging, were found to be significantly associated with an increased risk of combined clinical and imaging events. While the model estimated the risk of clinical or cerebral lesion progression to be approximately 0.5% per year when none of these factors was present, this risk exceeded 20% per year when all factors were present.ConclusionA simple combination of demographic, clinical, and cerebral perfusion imaging measures may aid in predicting the risk of incident stroke and cerebral lesion progression in adult patients with MMA. These results may help to improve therapeutic decisions and aid in the design of future trials in adults with this rare condition.
Published: 2018

45. Remission of depression in patients with schizophrenia and comorbid major depressive disorder: results from the FACE-SZ cohort

Author: Laurent Boyer, Franck Schürhoff, Christophe Lançon, A. Schandrin, Bruno Aouizerate, C. Passerieux, Thierry d'Amato, Delphine Capdevielle, Marion Leboyer, Julien Dubreucq, M. Andrianarisoa, N Coulon, Fabrice Berna, Guillaume Fond, Jasmina Mallet, Lore Brunel, Romain Rey, Ophélia Godin, Caroline Dubertret, Pierre-Michel Llorca, Pierre Vidailhet, Isabelle Chereau, David Misdrahi, Sylvain Leignier, Catherine Faget, E. Bulzacka, Mathieu Urbach, 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), Neurosciences sensorielles et cognitives (NSC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Université Pierre et Marie Curie - Paris 6 (UPMC), Fondation FondaMental [Créteil], Hôpital Charles Perrens, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de psychiatrie, CHU Clermont-Ferrand, Psychopathologie et neurobiologie de la schizophrénie et de la vulnérabilité à la psychose, Centre Hospitalier le Vinatier [Bron]-IFR19-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Service de Psychiatrie D Adultes, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Neuropsychologie Cognitive et Prise en Charge des Troubles de la Communication Schizophreniques, Institut National de la Santé et de la Recherche Médicale (INSERM), FondaMental Foundation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Albert Chenevier-Fondation de Coopération Scientifique, 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 (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre hospitalier Charles Perrens [Bordeaux], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR19-Centre Hospitalier le Vinatier [Bron], Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants ( SPMC ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Aix Marseille Université ( AMU ), Fédération de Médecine Translationnelle de Strasbourg ( FMTS ), Université de Strasbourg ( UNISTRA ), Universite ́ Pierre et Marie Curie-Paris, F-75005, Paris, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 ( UCBL ), Université Grenoble Alpes - UFR Médecine ( UGA UFRM ), Université Grenoble Alpes ( UGA ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Neuropsychologie Cognitive et prise en Charge des Troubles de la Communication schizophréniques, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Albert Chenevier-Fondation de Coopération Scientifique, 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 ), and CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA )
Subjects: Male, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Comorbidity, Cohort Studies, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0302 clinical medicine, Prevalence, ComputingMilieux_MISCELLANEOUS, Depression (differential diagnoses), [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Remission Induction, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Antidepressive Agents, 3. Good health, Psychiatry and Mental health, Schizophrenia, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Major depressive disorder, Antidepressant, Female, France, medicine.symptom, Adult, medicine.medical_specialty, behavioral disciplines and activities, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Young Adult, 03 medical and health sciences, Delusion, Internal medicine, mental disorders, medicine, Humans, Antipsychotic, Avolition, Psychiatric Status Rating Scales, Depressive Disorder, Major, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Odds ratio, medicine.disease, 030227 psychiatry, Logistic Models, Multivariate Analysis, Quality of Life, business, 030217 neurology & neurosurgery
Abstract: BackgroundMajor depressive disorder (MDD) is underdiagnosed and undertreated in schizophrenia, and has been strongly associated with impaired quality of life.AimsTo determine the prevalence and associated factors of MDD and unremitted MDD in schizophrenia, to compare treated and non-treated MDD.MethodParticipants were included in the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment. MDD was defined by a Calgary score ≥6. Non-remitted MDD was defined by current antidepressant treatment (unchanged for >8 weeks) and current Calgary score ≥6.Results613 patients were included and 175 (28.5%) were identified with current MDD. MDD has been significantly associated with respectively paranoid delusion (odds ratio 1.8; P = 0.01), avolition (odds ratio 1.8; P = 0.02), blunted affect (odds ratio 1.7; P = 0.04) and benzodiazepine consumption (odds ratio 1.8; P = 0.02). Antidepressants were associated with lower depressive symptoms score (5.4 v. 9.5; P < 0.0001); however, 44.1% of treated patients remained in non-remittance MDD. Nonremitters were found to have more paranoid delusion (odds ratio 2.3; P = 0.009) and more current alcohol misuse disorder (odds ratio 4.8; P = 0.04). No antidepressant class or specific antipsychotic were associated with higher or lower response to antidepressant treatment. MDD was associated with Metabolic syndrome (31.4 v. 20.2%; P = 0.006) but not with increased C-reactive protein.ConclusionsAntidepressant administration is associated with lower depressive symptom level in patients with schizophrenia and MDD. Paranoid delusions and alcohol misuse disorder should be specifically explored and treated in cases of non-remission under treatment. MetS may play a role in MDD onset and/or maintenance in patients with schizophrenia.Declaration of interestNone.
Published: 2018
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46. Trajectoire du trouble bipolaire en fonction de sa séquence d’installation avec les troubles liés à l’usage d’alcool dans la cohorte des centres experts du réseau fondamental : identifier des cibles thérapeutiques

Author: R. Belzeaux, J. Loftus, I. Biseul, G. Brousse, S. Guillaume, Romain Icick, S. Gard, Ophélia Godin, L. Samalin, Groupe d’étude BIPolaire-ADDiction, and Valerie Aubin
Abstract: L’usage et les troubles lies a l’usage de substances (TUS) sont la regle dans le trouble bipolaire (TB). Ils pejorent le pronostic du TB en aggravant les decompensations thymiques, en diminuant la reponse au traitement usuel et, surtout, en augmentant la mortalite toutes causes. L’epidemiologie descriptive des comorbidites addictives du TB est desormais mieux connue [1] , [2] , mais on connait mal l’influence de l’apparition ou de la remission des TUS sur l’evolution du TB, qui presente de probables specificites pronostiques par substance et selon la sequence d’installation [3] . Nous nous focaliserons sur la comorbidite entre TB et troubles lies a l’usage d’alcool (TUA), qui aggravent la polarite depressive du TB, le risque de cancer et, probablement, de suicide. Ces TUA concernent 20 % des 2945 participants de la cohorte du reseau national des centres experts du trouble bipolaire de la fondation Fondamental dont les donnees anonymisees sont disponibles. Les participants, diagnostiques TB1 (52 %) ou TB2 (48 %) (nous avons exclu les TB-NOS pour notre projet), sont a 61 % des femmes et leur âge moyen est de 41 ± 13 ans. Les âges de debut des TUA, contrairement a tabac et cannabis, ont une distribution multimodale tres etalee permettant l’etude de trois sous-groupes d’interet par des modeles multivaries stratifies sur le genre TUA precedant largement le TB, TUA et TB relativement concomitants, et TUA debutant largement apres le TB. Notre hypothese est que ces groupes ne montrent pas (1) la meme evolution du TB evaluee retrospectivement par le taux annuel d’episodes thymiques, le nombre de comorbidites addictives et le fonctionnement a l’inclusion (Romain ICICK) et (2) influencent differemment les symptomes anxieux et thymiques ainsi que le traitement medicamenteux du TB evalues prospectivement a un an (Ludovic SAMALIN). Pour conclure, Isabelle Biseul presentera une lecture critique des donnees de la litterature concernant les possibilites therapeutiques pour les patients avec TB + TUA, en interrogeant notamment leurs benefices sur l’usage d’alcool, l’humeur, ou les deux. Puis elle decrira les resultats encourageants d’un programme de therapie cognitive de groupe specifique developpe dans un centre expert parisien [4] . Ces presentations fourniront a l’auditoire une base solide pour discuter la prise en charge integree et personnalisee des individus souffrant d’une comorbidite TB + TUA, situation deletere et particulierement frequente.
Published: 2019
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47. Étude rétrospective de la trajectoire du trouble bipolaire en fonction de l’ordre et du délai d’apparition avec un trouble lié à l’usage d’alcool

Author: Romain Icick, Groupe d’étude BIPolaire-ADDiction, Valerie Aubin, R. Belzeaux, Ophélia Godin, J. Loftus, S. Gard, L. Samalin, G. Brousse, S. Guillaume, and I. Biseul
Abstract: Les patients souffrant de trouble bipolaire (TB) ont un risque augmente de souffrir egalement d’un trouble lie a l’usage d’alcool (AUD), qui pejore le pronostic du TB en augmentant notamment les symptomes depressifs et le risque suicidaire. La physiopathologie de cette comorbidite reste mal connue, meme si TB et AUD partagent certains facteurs de risque, notamment temperamentaux et environnementaux precoces. Le developpement de cette comorbidite pourrait avoir des consequences majeures sur la trajectoire des patients concernes, aussi bien en fonction de la sequence d’apparition des troubles que de leur delai de survenue respective. Les donnees de la litterature indiquent que la sequence « AUD puis TB » est associee a un âge plus eleve, a d’autres comorbidites addictives, au genre masculin et a la presence de troubles anxieux comorbides. Cependant, les donnees existantes n’ont pas evalue l’influence potentielle du delai d’apparition des deux troubles, ce que nous avons etudie au moyen d’analyses de survie appropriees chez 2515 patients diagnostiques TB-I ou TB-II dans les centres experts de la fondation Fondamental. Nous avons analyse les caracteristiques associees (i) a la presence d’un AUD et a sa sequence d’apparition avec le TB au moyen d’une regression multinomiale puis (ii) au delai de survenue entre les deux par un modele de survie. Nous avons confirme certaines caracteristiques associees a la presence d’un AUD : comorbidites addictives, troubles anxieux, debut maniaque du TB, genre masculin et augmentation de la prevalence des tentatives de suicide. Nous avons surtout pu mettre en avant : (i) que les trajectoires cliniques des patients comorbides sont surtout liees a l’âge de debut du TB, qui est toujours plus tardif en cas de sequence « AUD puis TB » comparee a « TB puis AUD », ces patients ayant ainsi des scores plus eleves de depression, (ii) : que ces resultats ont une portee methodologique et clinique importante concernant le reperage des comorbidites addictives chez les patients souffrant de TB et sur les priorites a donner dans le soin des patients souffrant de telles comorbidites.
Published: 2019
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48. Longitudinal Association of Carotid Plaque Presence and Intima-Media Thickness With Depressive Symptoms in the Elderly

Author: Catherine Helmer, Jean-Philippe Empana, Karen Ritchie, Christof Prugger, Carole Dufouil, Christophe Tzourio, Ophélia Godin, and Marie-Cécile Perier
Subjects: Male, medicine.medical_specialty, Urban Population, Carotid Artery, Common, Comorbidity, Carotid Intima-Media Thickness, Severity of Illness Index, Age Distribution, Internal medicine, medicine.artery, Odds Ratio, Prevalence, medicine, Humans, Carotid Stenosis, Longitudinal Studies, Prospective Studies, Common carotid artery, Sex Distribution, Geriatric Assessment, Depression (differential diagnoses), Aged, Subclinical infection, Aged, 80 and over, Depression, Vascular disease, business.industry, Center for Epidemiologic Studies Depression Scale, Prognosis, medicine.disease, Plaque, Atherosclerotic, Confidence interval, Surgery, Intima-media thickness, Cohort, Female, France, Cardiology and Cardiovascular Medicine, business
Abstract: Objective— To investigate prospectively whether subclinical vascular disease is associated with future depressive symptoms in the elderly. Approach and Results— A multicenter cohort of community-dwelling individuals aged 65 to 85 years was examined for carotid plaque presence and common carotid artery intima-media thickness at baseline and followed up after 2, 4, 7, and 10 years. At baseline and follow-up examinations, depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). High level of depressive symptoms was defined as a CES-D score >16 in men and >22 in women. Among 4125 participants (58% women) at baseline, men more frequently showed carotid plaque presence and had higher mean common carotid artery intima-media thickness than women. After adjustment for major cardiovascular risk factors, carotid plaque presence was associated with a higher CES-D score at the 10-year follow-up in men (+1.46; 95% confidence interval, 0.71–2.20; P P =0.022), but not in women. One SD increase in log-transformed common carotid artery intima-media thickness was associated with a higher CES-D score at the 10-year follow-up in women (+0.55; 95% confidence interval, 0.16–0.95; P =0.006) and men (+0.40; 95% confidence interval, 0.02–0.78; P =0.037). Common carotid artery intima-media thickness did not increase the likelihood of high level of depressive symptoms at follow-up in both sexes. Conclusions— Subclinical vascular disease is associated with the progression of depressive symptoms in elderly men and women and the occurrence of high level of depressive symptoms in elderly men.
Published: 2015
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49. Self-reported pain in patients with schizophrenia. Results from the national first-step FACE-SZ cohort

Author: Laurent Boyer, Christine Passerieux, Pierre Vidailhet, Delphine Capdevielle, Thierry d'Amato, A. Schandrin, Lore Brunel, Isabelle Chereau, N Coulon, Bruno Aouizerate, David Misdrahi, E. Bulzacka, Catherine Faget, Sylvain Leignier, Julien Dubreucq, Guillaume Fond, Franck Schürhoff, Mathieu Urbach, M. Andrianarisoa, Caroline Dubertret, Marion Leboyer, Pierre-Michel Llorca, Christophe Lançon, Jasmina Mallet, Hélène Denizot, Romain Rey, Ophélia Godin, Fabrice Berna, 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 d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Fondation FondaMental [Créteil], Université Pierre et Marie Curie - Paris 6 (UPMC), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Hôpital Charles Perrens, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de psychiatrie, CHU Clermont-Ferrand, Psychopathologie et neurobiologie de la schizophrénie et de la vulnérabilité à la psychose, Centre Hospitalier le Vinatier [Bron]-IFR19-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Psychiatrie D Adultes, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Neuropsychologie Cognitive et Prise en Charge des Troubles de la Communication Schizophreniques, Institut National de la Santé et de la Recherche Médicale (INSERM), FondaMental Foundation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Albert Chenevier-Fondation de Coopération Scientifique, 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 (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut National de la Santé et de la Recherche Médicale, AP-HM, Fondation FondaMental, Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants ( SPMC ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Aix Marseille Université ( AMU ), Universite ́ Pierre et Marie Curie-Paris, F-75005, Paris, Fédération de Médecine Translationnelle de Strasbourg ( FMTS ), Université de Strasbourg ( UNISTRA ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-IFR19-Centre Hospitalier le Vinatier [Bron], Université Grenoble Alpes - UFR Médecine ( UGA UFRM ), Université Grenoble Alpes ( UGA ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Neuropsychologie Cognitive et prise en Charge des Troubles de la Communication schizophréniques, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Albert Chenevier-Fondation de Coopération Scientifique, 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 ), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre hospitalier Charles Perrens [Bordeaux], and Université Claude Bernard Lyon 1 (UCBL)
Subjects: Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.medical_treatment, Comorbidity, Anxiety, Childhood trauma, Cohort Studies, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Benzodiazepines, 0302 clinical medicine, Prevalence, ComputingMilieux_MISCELLANEOUS, Depression (differential diagnoses), media_common, Physical pain, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Depression, Headache, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Antidepressive Agents, 3. Good health, Adult Survivors of Child Adverse Events, Schizophrenia, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Cohort, Antidepressant, Female, medicine.symptom, Antipsychotic Agents, Adult, medicine.medical_specialty, medicine.drug_class, media_common.quotation_subject, Pain, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 03 medical and health sciences, Internal medicine, medicine, Humans, Antipsychotic, Biological Psychiatry, Pharmacology, Benzodiazepine, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Addiction, medicine.disease, 030227 psychiatry, Cross-Sectional Studies, Self Report, business, 030217 neurology & neurosurgery
Abstract: Introduction Little is known about perception of physical pain in schizophrenia (SZ). Some studies have suggested that patients with SZ may have an increased pain threshold, while others have suggested that patients with SZ may suffer from undetected and untreated high physical pain levels. The objectives of this study were (i) to investigate the prevalence of self-reported physical pain in stabilized SZ subjects, and (ii) to determine whether physical pain was associated with psychiatric characteristics and somatic comorbidities (iii) to determine whether antidepressants and benzodiazepine administration were associated with lower self-reported pain. Method 468 community-dwelling stable SZ subjects (73% men, mean aged 32 years) were recruited in the Schizophrenia Expert Center national network. Patients with moderate to extreme pain, assessed with the EQ5D-5L questionnaire, were classified as belonging to the “pain group”. Results 104 (22.2%) reported moderate to extreme pain levels. In multivariate analysis, pain has been associated with headache (OR = 2.63 [1.04–6.63], p = 0.04), higher anxiety (OR = 1.61 [1.18–2.21], p = 0.003), higher current depressive symptoms (OR = 1.09 [1.01–1.17], p = 0.03), history of childhood trauma (1.03 [1.01–1.06], p = 0.01) and older age (OR = 1.04 [1.01–1.07], p = 0.03), independently of current psychotic severity, sociodemographic variables, antipsychotic, antidepressant and benzodiazepine treatments. No association with addictive behaviors or illness characteristics has been found. Conclusion The present findings suggest that community-dwelling SZ outpatients report a high rate of self-reported physical pain, associated with headache, depression and anxiety and history of childhood trauma. Physical pain should be systematically assessed and specifically treated, when needed, in patients with SZ.
Published: 2018
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50. Clinical correlates of longitudinal MRI changes in CADASIL

Author: Dominique Hervé, Marco Duering, Hugues Chabriat, Martin Dichgans, Ophélia Godin, Yifeng Ling, François De Guio, Eric Jouvent, and Jean Pierre Guichard
Subjects: Adult, Male, medicine.medical_specialty, Trail Making Test, CADASIL, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Internal medicine, medicine, Humans, Longitudinal Studies, Prospective Studies, skin and connective tissue diseases, Stroke, Receptor, Notch3, Cerebral atrophy, medicine.diagnostic_test, business.industry, Brain, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Hyperintensity, Neurology, Mutation, Cardiology, Disease Progression, Original Article, Dementia, Female, Neurology (clinical), sense organs, Atrophy, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Previous studies showed that various types of cerebral lesions, as assessed on MRI, largely contribute to the clinical severity of CADASIL. However, the clinical impact of longitudinal changes of classical markers of small vessel disease on conventional MRI has been only poorly investigated. One hundred sixty NOTCH3 mutation carriers (mean age ± SD, 49.8 ± 10.9 years) were followed over three years. Validated methods were used to determine the percent brain volume change (PBVC), number of incident lacunes, change of volume of white matter hyperintensities and change of number of cerebral microbleeds. Multivariable logistic regression analyses were performed to assess the independent association between changes of these MRI markers and incident clinical events. Mixed-effect multiple linear regression analyses were used to assess their association with changes of clinical scales. Over a mean period of 3.1 ± 0.2 years, incident lacunes are found independently associated with incident stroke and change of Trail Making Test Part B. PBVC is independently associated with all incident events and clinical scale changes except the modified Rankin Scale at three years. Our results suggest that, on conventional MRI, PBVC and the number of incident lacunes are the most sensitive and independent correlates of clinical worsening over three years in CADASIL.
Published: 2018

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