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Chronic low-grade peripheral inflammation is associated with ultra resistant schizophrenia. Results from the FACE-SZ cohort

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Abstract

A high rate of patients with schizophrenia (SZ) does not sufficiently respond to antipsychotic medication, which is associated with relapses and poor outcomes. Chronic peripheral inflammation has been repeatedly associated with schizophrenia risk and particularly to poor responders to treatment as usual with cognitive impairment in SZ subjects. The objective of present study was to confirm if ultra resistance to treatment in schizophrenia (UTRS) was associated to chronic peripheral inflammation in a non-selected sample of community-dwelling outpatients with schizophrenia. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. Current psychotic symptomatology was evaluated by the Positive and Negative Syndrome scale for Schizophrenia (PANSS). UTRS was defined by current clozapine treatment + PANSS total score ≥ 70. Functioning was evaluated by the Global Assessment of Functioning scale. High sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. 609 stabilized community-dwelling SZ subjects (mean age = 32.5 years, 73.6% male gender) have been included. 60 (9.9%) patients were classified in the UTRS group. In multivariate analyses, UTRS has been associated independently with chronic peripheral inflammation (OR = 2.6 [1.2–5.7], p = 0.01), illness duration (0R = 1.1 [1.0–1.2], p = 0.02) and impaired functioning (OR = 0.9 [0.9–0.9], p = 0.0002) after adjustment for age, sex, current daily tobacco smoking, metabolic syndrome and antidepressant consumption. Peripheral low-grade inflammation is associated with UTRS. Future studies should explore if anti-inflammatory strategies are effective in UTRS with chronic low-grade peripheral inflammation.

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Acknowledgements

This work was funded by AP-HM (Assistance Publique des Hôpitaux de Marseille), Fondation FondaMental (RTRS Santé Mentale), by the Investissements d’Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01. We express all our thanks to the nurses, and to the patients who were included in the present study. We thank Hakim Laouamri, and his team (Stéphane Beaufort, Seif Ben Salem, Karmène Souyris, Victor Barteau and Mohamed Laaidi) for the development of the FACE-SZ computer interface, data management, quality control and regulatory aspects.

Collaborators for the FACE-SZ Group

M. Andrianarisoa, B. Aouizerate, MD PhD, F. Berna, MD PhD, O. Blanc, Msc, L. Brunel, Msc, E. Bulzacka, Msc, D. Capdevielle, MD PhD, I. Chereau-Boudet, MD, G. Chesnoy-Servanin, Msc, J. M. Danion, MD, T. D’Amato, MD, PhD, A. Deloge, MD PhD, C. Delorme, Msc, H. Denizot, MD, J. M. Dorey, MD, C. Dubertret, MD, PhD, J. Dubreucq, MD, C. Faget, MD, C. Fluttaz, Msc, G. Fond, MD, S. Fonteneau, Msc, F. Gabayet, Msc, E. Giraud-Baro, MD, M. C. Hardy-Bayle, MD PhD, D. Lacelle, Msc, C. Lançon, MD PhD, H. Laouamri, Msc, M. Leboyer, MD PhD, T. Le Gloahec, Msc, Y. Le Strat, MD PhD, P. M. Llorca, MD PhD, J. Mallet, E. Metairie, Msc, D. Misdrahi, MD, I. Offerlin-Meyer, PhD, C. Passerieux, MD PhD, P. Peri, Msc, S. Pires, Msc, C. Portalier, Msc, L. Ramet, Msc, R. Rey, MD, C. Roman, Msc, M. Sebilleau, Msc, A. Schandrin, MD, F. Schürhoff, MD PhD, A. Tessier, Msc, A. M. Tronche, MD, M. Urbach, MD, F. Vaillant, Msc, A. Vehier, Msc, P. Vidailhet, MD PhD, E. Vilà, Msc, H. Yazbek, PhD, A. Zinetti-Bertschy, Msc.

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Authors and Affiliations

  1. Fondation FondaMental, Créteil, France

    G. Fond, O. Godin, L. Boyer, F. Berna, M. Andrianarisoa, N. Coulon, L. Brunel, E. Bulzacka, B. Aouizerate, D. Capdevielle, I. Chereau, T. D’Amato, C. Dubertret, J. Dubreucq, C. Faget, S. Leignier, C. Lançon, J. Mallet, D. Misdrahi, C. Passerieux, R. Rey, A. Schandrin, M. Urbach, P. M. Llorca, F. Schürhoff, M. Leboyer & M. Andrianarisoa

  2. INSERM U955, équipe de psychiatrie translationnelle, Créteil, France

    O. Godin, M. Andrianarisoa, N. Coulon, L. Brunel, E. Bulzacka, F. Schürhoff & M. Leboyer

  3. Université Paris-Est Créteil, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, Créteil, France

    O. Godin, M. Andrianarisoa, N. Coulon, L. Brunel, E. Bulzacka, F. Schürhoff & M. Leboyer

  4. Faculté de Médecine - Secteur Timone, Aix-Marseille Univ, EA 3279: CEReSS - Centre d’Etude et de Recherche sur les Services de Santé et la Qualité de vie, 27 Boulevard Jean Moulin, 13005, Marseille, France

    G. Fond & L. Boyer

  5. Centre Hospitalier Charles Perrens, Université de Bordeaux, 33076, Bordeaux, France

    B. Aouizerate & D. Misdrahi

  6. Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France

    F. Berna, P. Vidailhet & M. Andrianarisoa

  7. Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France

    D. Capdevielle & A. Schandrin

  8. CMP B, CHU, EA 7280 Faculté de Médecine, Université d’Auvergne, BP 69, 63003, Clermont-Ferrand Cedex 1, France

    I. Chereau & P. M. Llorca

  9. INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, Université Claude Bernard Lyon 1, Equipe PSYR2, Centre Hospitalier Le Vinatier, Pole Est, 95 bd Pinel, BP 30039, 69678, Bron Cedex, France

    T. D’Amato & R. Rey

  10. AP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, Inserm U894, Sorbonne Paris Cité, Faculté de médecine, Université Paris Diderot, Paris, France

    C. Dubertret & J. Mallet

  11. Centre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France

    J. Dubreucq & S. Leignier

  12. Assistance Publique des Hôpitaux de Marseille (AP-HM), Pôle Universitaire de Psychiatrie, Marseille, France

    C. Faget & C. Lançon

  13. Service de psychiatrie d’adulte, Centre Hospitalier de Versailles, UFR des Sciences de la Santé Simone Veil, Université Versailles Saint-Quentin en Yvelines, Versailles, France

    C. Passerieux & M. Urbach

  14. INRA, NutriNeuro, University of Bordeaux, U1286, 33076, Bordeaux, France

    B. Aouizerate

  15. CNRS UMR 5287-INCIA, Université de Bordeaux, Bordeaux, France

    D. Misdrahi

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  1. G. Fond
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  2. O. Godin
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  3. L. Boyer
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  4. F. Berna
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  5. M. Andrianarisoa
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  6. N. Coulon
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  7. L. Brunel
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  8. E. Bulzacka
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  9. B. Aouizerate
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  10. D. Capdevielle
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  11. I. Chereau
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  12. T. D’Amato
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  13. C. Dubertret
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  14. J. Dubreucq
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  15. C. Faget
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  16. S. Leignier
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  17. C. Lançon
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  18. J. Mallet
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  19. D. Misdrahi
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  20. C. Passerieux
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  21. R. Rey
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  22. A. Schandrin
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  23. M. Urbach
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  24. P. Vidailhet
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  25. P. M. Llorca
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  26. F. Schürhoff
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  27. M. Leboyer
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Consortia

the FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) Group

  • M. Andrianarisoa
  • , B. Aouizerate
  • , N. Bazin
  • , F. Berna
  • , O. Blanc
  • , L. Brunel
  • , E. Bulzacka
  • , D. Capdevielle
  • , I. Chereau-Boudet
  • , G. Chesnoy-Servanin
  • , J. M. Danion
  • , T. D’Amato
  • , A. Deloge
  • , C. Delorme
  • , H. Denizot
  • , J. M. Dorey
  • , C. Dubertret
  • , J. Dubreucq
  • , C. Faget
  • , C. Fluttaz
  • , G. Fond
  • , S. Fonteneau
  • , F. Gabayet
  • , E. Giraud-Baro
  • , M. C. Hardy-Bayle
  • , D. Lacelle
  • , C. Lançon
  • , H. Laouamri
  • , M. Leboyer
  • , T. Le Gloahec
  • , Y. Le Strat
  • , P. M. Llorca
  • , J. Mallet
  • , E. Metairie
  • , D. Misdrahi
  • , I. Offerlin-Meyer
  • , C. Passerieux
  • , P. Peri
  • , S. Pires
  • , C. Portalier
  • ,  L. Ramet
  • , R. Rey 
  • , C. Roman
  • , M. Sebilleau
  • , A. Schandrin
  • , F. Schürhoff
  • , A. Tessier
  • , A. M. Tronche
  • , M. Urbach
  • , F. Vaillant
  • , A. Vehier
  • , P. Vidailhet
  • , E. Vilà
  • , H. Yazbek
  •  & A. Zinetti-Bertschy

Contributions

GF and LB performed the statistical analysis. GF, LB, FS and ML wrote the first complete manuscript. GF, LB, FS and ML edited earlier versions of the manuscript for important intellectual content. All authors were involved in the patients’ recruitment, the clinical evaluation, acquisition of the clinical data, modified the manuscript and approved the final version.

Corresponding author

Correspondence to G. Fond.

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Conflict of interest

None.

Additional information

The members of the FACE-SZ Group are listed in “Acknowledgment”.

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Fond, G., Godin, O., Boyer, L. et al. Chronic low-grade peripheral inflammation is associated with ultra resistant schizophrenia. Results from the FACE-SZ cohort. Eur Arch Psychiatry Clin Neurosci 269, 985–992 (2019). https://doi.org/10.1007/s00406-018-0908-0

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  • DOI: https://doi.org/10.1007/s00406-018-0908-0

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