Immune signatures of treatment resistant schizophrenia: a FACE-SZ study Running title: Immune profile of treatment-resistant schizophrenia - Neuropsychiatrie- Recherche épidémiologique et clinique (U1061) Access content directly
Journal Articles Schizophrenia Bulletin Open Year : 2021

Immune signatures of treatment resistant schizophrenia: a FACE-SZ study Running title: Immune profile of treatment-resistant schizophrenia

Emilie Terro
  • Function : Author
Wahid Boukouaci
  • Function : Author
Ching-Lieng Lu
  • Function : Author
Fabrice Berna
  • Function : Author
Caroline Barau
  • Function : Author
Delphine Capdevielle
  • Function : Author
Julie Clauss-Kobayashi
  • Function : Author
Isabelle Chereau
  • Function : Author
Thierry d'Amato
  • Function : Author
Caroline Dubertret
  • Function : Author
Julien Dubreucq
Guillaume Fond
Hakim Laouamri
  • Function : Author
Sylvain Leignier
  • Function : Author
Christophe Lancon
  • Function : Author
Pierre-Michel Llorca
Jasmina Mallet
Philippe Le Corvoisier
Christine Passerieux
  • Function : Author
S. Parola
  • Function : Author
Baptiste Pignon
Mathieu Urbach
  • Function : Author
Andrei Szoke
  • Function : Author
Ryad Tamouza
Franck Schürhoff
  • Function : Author
  • PersonId : 937738

Abstract

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.
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Dates and versions

hal-03347951 , version 1 (27-01-2023)

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Marion Leboyer, Ophélia Godin, Emilie Terro, Wahid Boukouaci, Ching-Lieng Lu, et al.. Immune signatures of treatment resistant schizophrenia: a FACE-SZ study Running title: Immune profile of treatment-resistant schizophrenia. Schizophrenia Bulletin Open, 2021, 2 (1), pp.sgab012. ⟨10.1093/schizbullopen/sgab012⟩. ⟨hal-03347951⟩
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