1. Immune Signatures of Treatment-Resistant Schizophrenia: A FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) Study
- Author
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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