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1. 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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2. 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

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

Author

Eric Brunet-Gouet, Romain Rey, Christine Passerieux, Mathieu Urbach, Roxana-Mihaela Honciuc, Anne-Lise Bohec, Delphine Capdevielle, Sylvain Leigner, Myrtille André, Caroline Dubertret, Guillaume Fond, David Misdrahi, H. Laouamri, Bruno Aouizerate, Isabelle Chereau, Baptiste Pignon, Julien Dubreucq, Paul Roux, Julie Clauss, Fabrice Berna, Franck Schürhoff, Jasmina Mallet, Mickael Ehrminger, Christophe Lançon, Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier de Versailles André Mignot (CHV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Fondation FondaMental [Créteil], Département de psychiatrie adulte, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital La Colombière, Hôpital Charles Perrens, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Les Hôpitaux Universitaires de Strasbourg (HUS), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Clermont-Ferrand, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Diderot - Paris 7 (UPD7), CHU Grenoble, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), Centre de recherche en neurosciences de Lyon (CRNL), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre hospitalier Charles Perrens [Bordeaux], Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)

Subjects
mediation analyses, Mediation (statistics), structural equation modeling, Structural equation modeling, Cohort Studies, 03 medical and health sciences, Cognition, 0302 clinical medicine, Quality of life, medicine, Humans, Applied Psychology, Cognitive reserve, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Mechanism (biology), medicine.disease, humanities, 030227 psychiatry, Psychiatry and Mental health, Cross-Sectional Studies, quality of life, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Schizophrenic Psychology, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract

BackgroundThe determinants of quality of life (QoL) in schizophrenia are largely debated, mainly due to methodological discrepancies and divergence about the concepts concerned. As most studies have investigated bi- or tri-variate models, a multivariate model accounting for simultaneous potential mediations is necessary to have a comprehensive view of the determinants of QOL. We sought to estimate the associations between cognitive reserve, cognition, functioning, insight, depression, schizophrenic symptoms, and QoL in schizophrenia and their potential mediation relationships.MethodsWe used structural equation modeling with mediation analyses to test a model based on existing literature in a sample of 776 patients with schizophrenia from the FondaMental Foundation FACE-SZ cohort.ResultsOur model showed a good fit to the data. We found better functioning to be positively associated with a better QoL, whereas better cognition, better insight, higher levels of depression, and schizophrenic symptoms were associated with a lower QoL in our sample. Cognitive reserve is not directly linked to QoL, but indirectly in a negative manner via cognition. We confirm the negative relationship between cognition and subjective QoL which was previously evidenced by other studies; moreover, this relationship seems to be robust as it survived in our multivariate model. It was not explained by insight as some suggested, thus the mechanism at stake remains to be explained.ConclusionThe pathways to subjective QoL in schizophrenia are complex and the determinants largely influence each other. Longitudinal studies are warranted to confirm these cross-sectional findings.

Published
2020

4. 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

5. Factors associated with direct health care costs in schizophrenia: Results from the FACE-SZ French dataset

Author

Guillaume Fond, Marion Leboyer, Catherine Faget, Mathieu Urbach, Karine Chevreul, Romain Rey, C. Lançon, Pierre Vidailhet, F. Schürhoff, Jean-Michel Dorey, David Misdrahi, I. Chereau-Boudet, Delphine Capdevielle, Bruno Aouizerate, Sylvain Leigner, Julien Dubreucq, Myrtille André, Jasmina Mallet, Paul Roux, Pierre-Michel Llorca, Caroline Dubertret, Fabrice Berna, Amélie Prigent, Alice Plas, Charles Laidi, Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut 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), Fondation FondaMental [Créteil], Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital H. Mondor - A. Chenevier, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris]-Université Paris Diderot - Paris 7 (UPD7), Hôtel-Dieu, Département de psychiatrie adulte, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital La Colombière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Cross-sectional study, Cost, Schizophrenia (object-oriented programming), [SDV]Life Sciences [q-bio], Psychological intervention, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cost of Illness, Health care, Medicine, Humans, Schizophernia, Pharmacology (medical), 030212 general & internal medicine, Cognitive rehabilitation therapy, Psychiatry, Socioeconomic status, Biological Psychiatry, health care economics and organizations, Pharmacology, business.industry, Medico-economic, Health Care Costs, Middle Aged, 030227 psychiatry, 3. Good health, Hospitalization, Psychiatry and Mental health, Cross-Sectional Studies, Neurology, Cohort, Schizophrenia, Female, Neurology (clinical), France, business, Cohort study
Abstract

International audience; INTRODUCTION: There is a lack of data on health care consumption of patients suffering from schizophrenia, as well as on the related health care costs. Factors associated with health care costs have not been widely studied, whereas knowledge on this topic would allow identifying risk factors and delineating strategies to improve patients' health and follow-up, likely to also decrease health care costs. The aim of this study was to estimate the average direct health care cost of patients with schizophrenia in France and to identify the factors associated with this cost. METHODS: The study population included patients with schizophrenia enrolled in the FondaMental Advanced Centers of Expertise for Schizophrenia cohort. We accounted for the costs directly related to the treatment of schizophrenia. They included the costs of hospitalizations (full- and part-time), psychiatric ambulatory consultations and medications. We studied three categories of factors potentially associated with direct health care costs: demographic, socioeconomic and clinical characteristics. RESULTS: Three hundred and ninety five patients with schizophrenia were included. The mean (median) annual direct health care cost per patient amounted to \texteuro14,995 (\texteuro3,435). A lower level of functioning and being single were associated with a higher cost. A significant association between the expert center of inclusion and the direct health care cost of schizophrenia was also highlighted. CONCLUSION: Our results highlighted the significant cost of schizophrenia and suggest that improvement in patient care, based on well-validated targeted therapeutic interventions such as psycho-education and cognitive rehabilitation, could reduce worsening in symptom severity and therefore decrease health care costs.

Published
2018

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