Immune Signatures of Treatment-Resistant Schizophrenia: A FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) Study
Marion Leboyer, Ophélia Godin, Emilie Terro, Wahid Boukouaci, Ching-lieng Lu, Myrtille André, Bruno Aouizerate, Fabrice Berna, Caroline Barau, Delphine Capdevielle, Julie Clauss-Kobayashi, Isabelle Chéreau, Thierry d’Amato, Caroline Dubertret, Julien Dubreucq, Guillaume Fond, H. Laouamri, Sylvain Leignier, Christophe Lançon, Pierre‐Michel Llorca, Jasmina Mallet, Philippe Le Corvoisier, D. Misdrahi, Christine Passerieux, Romain Rey, Baptiste Pignon, Mathieu Urbach, Andreı̈ Szöke, Franck Schürhoff, Ryad Tamouza, Fabrice Berna, Émmanuel Haffen, Marion Leboyer, Pierre‐Michel Llorca, Franck Schürhoff, V. Barteau, S. Bensalem, Ophélia Godin, H. Laouamri, K. Souryis, Marion Leboyer, I. Offerlin-Meyer, Baptiste Pignon, Franck Schürhoff, Andreı̈ Szöke, Bruno Aouizerate, A. Deloge, D. Misdrahi, E Vilà, O. Blanc, Isabelle Chéreau, H. Denizot, R M Honciuc, Denis Lacelle, Pierre‐Michel Llorca, Sara Xavier Pires, Caroline Dubertret, Jasmina Mallet, C Portalier, Julien Dubreucq, C. Fluttaz, Franck Gabayet, Carlos R. Detrés Román, G. Chesnoy-Servanin, Thierry d’Amato, Jean‐Michel Dorey, Romain Rey, A. Vehier, Christophe Lançon, C Faget, E. Metairie, P Peri, F. Vaillant, Fabrice Berna, Pierre Vidailhet, A. Zinetti-Bertschy, Delphine Capdevielle, H. Yazbek, Stéphanie Esselin, M. Jarroir, Christine Passerieux, Mathieu Urbach
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.