Prediction of relapse in a French cohort of outpatients with schizophrenia (FACE-SZ): Prediction, not association.
Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2025-03-01; 137: 111304
DOI: 10.1016/j.pnpbp.2025.111304
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1. Prog Neuropsychopharmacol Biol Psychiatry. 2025 Feb 27;137:111304. doi:
10.1016/j.pnpbp.2025.111304. Online ahead of print.
Prediction of relapse in a French cohort of outpatients with schizophrenia
(FACE-SZ): Prediction, not association.
Barbosa S(1), Tamouza R(2), Leboyer M(2), Aouizerate B(3), Andrieu C(4), Andre
M(5), Boukouaci W(2), Capdevielle D(5), Chereau I(6), Kobayashi JC(7), Coulon
N(8), Dorey JM(9), Davidovic L(1), Dubertret C(10), Fakra E(11), Fond G(4), Goze
T(12), Khalfallah O(1), Leignier S(8), Llorca PM(6), Mallet J(10), Martinuzzi
E(1), Misdrahi D(13), Oriol N(11), Pignon B(2), Rey R(9), Roux P(14), Schürhoff
F(2), Schorr B(7), Urbach M(14), Very E(12), Wu CL(2), Benros M(15), Simon
J(16), Hasan A(17); FondaMental Academic Centers of Expertise for Schizophrenia
(FACE-SZ) collaborators; Glaichenhaus N(18), Godin O(19).
Author information:
(1)Université Côte d’Azur, Centre National de la Recherche Scientifique,
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
(2)Fondation FondaMental, Créteil, France; Université Paris Est Créteil (UPEC),
INSERM, Institut Henri Mondor the Recherche Biomédicale, Laboratoire
Neuro-Psychiatrie Translationnelle, Créteil, France; Assistance Publique
Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Département
Médico-Universitaire de Psychiatrie et d’Addictologie, Créteil, France.
(3)Fondation FondaMental, Créteil, France; University Department of General
Psychiatry, Charles Perrens Hospital, F-33076 Bordeaux, France; Laboratory of
Nutrition and Integrative Neurobiology (UMR INRA 1286), University of Bordeaux,
Bordeaux, France.
(4)Fondation FondaMental, Créteil, France; AP-HM, Service Universitaire de
psychiatrie et d’addictologie (Pr Lançon), Hôpital Sainte Marguerite, 13009
Marseille, France.
(5)Fondation FondaMental, Créteil, France; Service Universitaire de Psychiatrie
Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1,
Inserm, 1061 Montpellier, France.
(6)Fondation FondaMental, Créteil, France; University of Clermont Auvergne,
CMP-B CHU, CNRS, Clermont Auvergne INP, Institut Pascal, F-63000
Clermont-Ferrand, France.
(7)Fondation FondaMental, Créteil, France; Hôpitaux Universitaires de
Strasbourg, Université de Strasbourg, INSERM U1329, Fédération de Médecine
Translationnelle de Strasbourg, Strasbourg, France.
(8)Fondation FondaMental, Créteil, France; Centre Référent de Réhabilitation
Psychosociale et de Remédiation Cognitive (C3R), CH Alpes Isère, Grenoble,
France.
(9)Fondation FondaMental, Créteil, France; INSERM U1028, CNRS UMR5292, Centre de
Recherche en Neurosciences de Lyon, Université Claude Bernard Lyon 1, Equipe
PSYR2, Centre Hospitalier Le Vinatier, Pole Est, 95 bd Pinel, BP 30039, 69678
Bron Cedex, France.
(10)Fondation FondaMental, Créteil, France; AP-HP, Groupe
Hospitalo-universitaire AP-HP Nord, DMU ESPRIT, Service de Psychiatrie et
Addictologie, Hôpital Louis Mourier, Colombes, France; Université de Paris
Inserm UMR1266, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
(11)Fondation FondaMental, Créteil, France; Department of Psychiatry, University
Hospital of Saint-Etienne, Saint-Etienne, France.
(12)Fondation FondaMental, Créteil, France; Department of Psychiatry,
Psychotherapies, Art-therapy, Toulouse University Hospital; Equipe de Recherche
sur les Rationalités Philosophiques et les Savoirs – EA3051, Université de
Toulouse – Jean Jaurès, Toulouse, France.
(13)Fondation FondaMental, Créteil, France; University of Bordeaux, Aquitaine
Institute for Cognitive and Integrative Neuroscience (CNRS UMR 5287-INCIA),
Bordeaux, France; Department of Adult Psychiatry, Charles Perrens Hospital,
Bordeaux, France.
(14)Fondation FondaMental, Créteil, France; Versailles Hospital, Department of
Adult Psychiatry and Addictology, Centre Hospitalier de Versailles, 177 rue de
Versailles, 78157 Le Chesnay, France; DisAP-DevPsy-CESP, INSERM UMR1018,
University of Paris-Saclay; University of Versailles Saint-Quentin-En-Yvelines,
78000 Versailles, France.
(15)CORE-Copenhagen Research Centre for Mental Health, Mental Health Centre
Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
(16)Department of Health Economics, Center for Public Health, Medical University
of Vienna, Vienna, Austria; Department of Psychiatry, University of Oxford,
Oxford, UK.
(17)Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical
Faculty, University of Augsburg, Bezirkskrankenhaus Augsburg,
Geschwister-Schönert-Str. 1, 86156 Augsburg, Germany; DZPG (German Center for
Mental Health), partner site München/Augsburg, Augsburg, Germany.
(18)Université Côte d’Azur, Centre National de la Recherche Scientifique,
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France; Fondation
FondaMental, Créteil, France.
(19)Fondation FondaMental, Créteil, France; Université Paris Est Créteil (UPEC),
INSERM, Institut Henri Mondor the Recherche Biomédicale, Laboratoire
Neuro-Psychiatrie Translationnelle, Créteil, France. Electronic address:
.
BACKGROUND: Schizophrenia (SZ) commonly manifests through multiple relapses,
each impeding the path to recovery and incurring personal and societal costs.
Despite the identification of various risk factors associated to the risk of
relapse, the development of accurate algorithms predictive of relapse has been
limited, partly due to inadequate statistical methods. Additionally, despite the
wealth of data showing strong associations between inflammation and
schizophrenia, the two existing studies failed to demonstrate whether
inflammatory parameters could predict relapse. Our goal is then to identify
clinical and inflammatory parameters associated with relapse in schizophrenia
and to develop model to predict relapse in each patient.
METHODS: We have used classical Cox regression, survival penalized regression,
as well as survival random forests to analyze clinical and inflammatory
biological data collected in the network of the Schizophrenia Expert Centers in
France in which individuals with SZ are clinically assessed and followed up
annually for 3 years.
RESULTS: Among 247 individuals with SZ, 71 (29 %) experienced a psychotic
relapse during the 3-year follow-up period. The variables most consistently
associated with relapses were smoking status, severity of positive symptoms and
low global functioning. From a panel of inflammatory parameters, only IL-8 serum
levels were associated with time to relapse. The predictive performance,
assessed using C-index, was 0.54 using both penalized regression and random
forests.
CONCLUSIONS: We found several clinical and biological variables consistently
associated with relapses across three distinct statistical methods. However,
despite these associations, the predictive capacity of these models remained
low, highlighting that association does not necessarily mean prediction.
Copyright © 2024. Published by Elsevier Inc.
DOI: 10.1016/j.pnpbp.2025.111304
PMID: 40023308
Conflict of interest statement: Declaration of competing interest The authors
declare that they have no competing interests.