Pro-inflammatory processes and metabolic syndrome: combined risk of resistance to treatment in patients with schizophrenia from the FACE-SZ cohort.
Psychiatry Research. 2025-08-01; 350: 116557
DOI: 10.1016/j.psychres.2025.116557
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https://www.bordeaux-neurocampus.fr/11666
Saitoh K(1), Lajnef M(2), Boukouaci W(2), Andre M(3), Andrieu C(4), Aouizerate
B(5), Barau C(6), Bouassida J(2), Capdevielle D(3), Chereau I(7),
Clauss-Kobayashi J(8), Coulon N(9), Dorey JM(10), Dubertret C(11), Fakra E(12),
Fond G(4), Goze T(13), Le Corvoisier P(6), Leignier S(9), Llorca PM(7), Mallet
J(11), Misdrahi D(14), Oriol N(12), Pignon B(15), Rey R(10), Roux P(16),
Schürhoff F(15), Schorr B(8), Urbach M(16), Very E(13), Wu CL(2); FACE-SZ
(FondaMental Academic Centers of Expertise for Schizophrenia) collaborators;
Leboyer M(15), Godin O(2), Tamouza R(15).
Author information:
(1)Universite Paris Est Créteil (UPEC), INSERM U955, IMRB, Translational
Neuropsychiatry, DMU IMPACT, Fondation FondaMental, Créteil F-94010, France;
Fondation FondaMental, France. Electronic address: .
(2)Universite Paris Est Créteil (UPEC), INSERM U955, IMRB, Translational
Neuropsychiatry, DMU IMPACT, Fondation FondaMental, Créteil F-94010, France;
Fondation FondaMental, France.
(3)Fondation FondaMental, France; Service Universitaire de Psychiatrie Adulte,
Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm,
Montpellier 1061, France.
(4)Fondation FondaMental, France; AP-HM, Service Universitaire de Psychiatrie et
D’addictologie (Pr Lançon), Hôpital Sainte Marguerite, Marseille 13009, France.
(5)Fondation FondaMental, France; University Department of General Psychiatry,
Charles Perrens Hospital, Bordeaux F-33076, France; Laboratory of Nutrition and
Integrative Neurobiology (UMR INRA 1286), University of Bordeaux, Bordeaux,
France.
(6)Hôpitaux Universitaires Henri Mondor, Université Paris Est Créteil, Inserm,
Centre Investigation Clinique 1430, AP-HP, Créteil F94010, France.
(7)Fondation FondaMental, France; University of Clermont Auvergne, CMP-B CHU,
CNRS, Clermont Auvergne INP, Institut Pascal, Clermont-Ferrand F-63000, France.
(8)Fondation FondaMental, France; Hôpitaux Universitaires de Strasbourg,
Université de Strasbourg, INSERM U1329, Fédération de Médecine Translationnelle
de Strasbourg, Strasbourg, France.
(9)Fondation FondaMental, France; Centre Référent de Réhabilitation
Psychosociale et de Remédiation Cognitive (C3R), CH Alpes Isère, Bordeaux,
France.
(10)Fondation FondaMental, France; Centre de Recherche en Neurosciences de Lyon,
Université Claude Bernard Lyon 1, Equipe PSYR2, Centre Hospitalier Le Vinatier,
Pole Est, 95 bd Pinel, BP 30039INSERM U1028, CNRS UMR5292, Bron Cedex 69678,
France.
(11)Fondation FondaMental, France; DMU ESPRIT, Service de Psychiatrie et
Addictologie, Hôpital Louis Mourier, AP-HP, Groupe Hospitalo-universitaire AP-HP
Nord, Colombes, France; Université de Paris Inserm UMR1266, Sorbonne Paris Cité
Faculté de Médecine, France.
(12)Fondation FondaMental, France; Department of Psychiatry, University Hospital
of Saint-Etienne, Saint-Etienne, France.
(13)Fondation FondaMental, France; Department of Psychiatry, Psychotherapies,
Art-therapy, Université de Toulouse – Jean Jaurès, Toulouse University Hospital,
Equipe de Recherche sur les Rationalités Philosophiques et les Savoirs – EA3051,
Toulouse, France.
(14)Fondation FondaMental, France; University of Bordeaux, Aquitaine Institute
for Cognitive and Integrative Neuroscience (CNRS UMR 5287-INCIA), Department of
adult Psychiatry , Charles Perrens Hospital, Bordeaux, France.
(15)Universite Paris Est Créteil (UPEC), INSERM U955, IMRB, Translational
Neuropsychiatry, DMU IMPACT, Fondation FondaMental, Créteil F-94010, France;
Fondation FondaMental, France; AP-HP, Hôpitaux Universitaires Henri Mondor,
Département Médico-Universitaire de Psychiatrie et d’Addictologie (DMU IMPACT),
Fédération Hospitalo-Universitaire de Médecine de Précision en Psychiatrie (FHU
ADAPT), F-94010, France.
(16)Fondation FondaMental, France; Versaillles Hospital, Department of Adult
Psychiatry and Addictology, Versailles Hospital, Centre Hospitalier de
Versailles, 177 rue de Versailles Le Chesnay 78157, DisAP-DevPsy-CESP, INSERM
UMR1018, University of Paris-Saclay, University of Versailles
Saint-Quentin-En-Yvelines, 78000, Versailles, France.
Schizophrenia (SZ) is characterized by a variable clinical expression and course
peppered/hampered by severe complications. In particular, resistance to
treatment (overall-TRS, treatment resistant SZ including UTRS, ultra-TRS) and
metabolic syndrome (MetS) are highly prevalent, and both demonstrated to be
underpinned, at least partly, by pro-inflammatory processes. Given that such
processes also underlie SZ per se, we hypothesized that potential inter-twinning
between SZ- and MetS-related inflammatory processes may exert a combined effect
on the risk of having overall-TRS/UTRS. A total of 419 outpatients with SZ
underwent clinical assessments and blood sample collection. Using the values of
circulating levels of eleven cytokines, we built a ratio between pro- and
anti-inflammatory components respectively corresponding to the
immunoinflammatory response system (IRS) and the compensatory immunoregulatory
reflex system (CIRS) which overall reflect the underlying inflammatory status.
Such ratios allowed to categorize the patients according to Inflammation and
MetS on four categories as follow: Inflammation(+)MetS(+),
Inflammation(+)MetS(-), Inflammation(-)MetS(+) and Inflammation(-)MetS(-).
Multivariate logistic regression analysis showed that the combination of
inflammation and MetS modulate the risk of having the overall-TRS
[Inflammation(+)MetS(-): OR=2.28, 95 %CI [1.04-5.00], p = 0.039 and
Inflammation(+)MetS(+): OR=4.59, 95 % CI [1.76-11.97], p = 0.002 overall in
comparison to Inflammation(-)MetS(-)]. Moreover, we observed that individuals
with UTRS are those associated with both inflammation and/or MetS. Our results
demonstrated the potential combined effect of MetS and inflammation towards
resistance to treatment. Given that overall-TRS/UTRS are unpredictable while
both inflammation and MetS can be early detected and managed, our findings shed
new light on the possibility to better prevent treatment resistance in SZ.
Copyright © 2025 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.psychres.2025.116557
PMID: 40460461 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of competing interest The authors
declare no competing interests.