Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 27;2(1):sgab012.
doi: 10.1093/schizbullopen/sgab012. eCollection 2021 Jan.

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

Marion Leboyer  1   2   3 , Ophélia Godin  1   3 , Emilie Terro  3 , Wahid Boukouaci  2   3 , Ching-Lieng Lu  2   3 , Myrtille Andre  3   4 , Bruno Aouizerate  3   5   6 , Fabrice Berna  3   7 , Caroline Barau  8 , Delphine Capdevielle  3   4 , Julie Clauss-Kobayashi  3   7 , Isabelle Chereau  3   9 , Thierry D Amato  10 , Caroline Dubertret  3   11 , Julien Dubreucq  3   12 , Guillaume Fond  3   13 , Hakim Laouamri  3 , Sylvain Leignier  3   12 , Christophe Lancon  3   13 , Pierre-Michel Llorca  3   9 , Jasmina Mallet  3   11 , Philippe Le Corvoisier  8 , David Misdrahi  3   14 , Christine Passerieux  3   15 , Romain Rey  3   10 , Baptiste Pignon  1   2   3 , Mathieu Urbach  3   15 , Andrei Szoke  1   2   3 , Franck Schürhoff  1   2   3 , Ryad Tamouza  1   2   3 ; FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) Groups
Collaborators, Affiliations

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

Marion Leboyer et al. Schizophr Bull Open. .

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.

Keywords: clozapine; immuno-inflammatory; profile; schizophrenia; signatures; treatment-resistant.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Association between pro-inflammatory molecules (IL-17A, IL-6, IL-10, and B2M) along with the severity status of resistance. Abbreviations: TRS, treatment-resistant schizophrenia; UTRS, ultra treatment-resistant schizophrenia. *P-value < .05, **P-value < .005.
See this image and copyright information in PMC

References

    1. Howes OD, McCutcheon R, Agid O, et al. . Treatment-resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017;174(3):216–229. - PMC - PubMed
    1. Kuipers E, Yesufu-Udechuku A, Taylor C, Kendall T. Management of psychosis and schizophrenia in adults: summary of updated NICE guidance. BMJ. 2014;348:g1173. - PubMed
    1. Kennedy JL, Altar CA, Taylor DL, Degtiar I, Hornberger JC. The social and economic burden of treatment-resistant schizophrenia: a systematic literature review. Int Clin Psychopharmacol. 2014;29(2):63–76. - PubMed
    1. Howes OD, Vergunst F, Gee S, McGuire P, Kapur S, Taylor D. Adherence to treatment guidelines in clinical practice: study of antipsychotic treatment prior to clozapine initiation. Br J Psychiatry. 2012;201(6):481–485. - PubMed
    1. Yoshimura B, Yada Y, So R, Takaki M, Yamada N. The critical treatment window of clozapine in treatment-resistant schizophrenia: secondary analysis of an observational study. Psychiatry Res. 2017;250:65–70. - PubMed