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Relationships between low-grade peripheral inflammation and psychotropic drugs in schizophrenia: results from the national FACE-SZ cohort

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Abstract

Low-grade inflammation has repeatedly been associated with schizophrenia (SZ) and in particular with cognitive impairment. Female gender, overweight and tobacco smoking have been suggested as risk factors to increase inflammation while preclinical inconsistent findings have been found regarding the association with psychotropic drugs. The aim of this study was to explore if psychotropic drugs were associated with inflammation in SZ and to determine which psychotropic drug was associated with inflammation in stable SZ subjects while considering clinical confounding factors. 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. High-sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. The zero-inflated Poisson regression model estimated the relationship between low-grade inflammation and psychotropic drug. Four hundred and five stabilized, community-dwelling SZ subjects (mean age = 32.6 years, 74% male gender) have been included. In total, 148 participants (36.5%) were found with undetectable blood hs-CRP level. The probability of having an undetectable CRP was associated with a lower body mass index (p < 0.0001) and no cyamemazine add-on antipsychotic therapy (p = 0.001). The other 257 participants (63.5%) were found to have low-grade inflammation (hs-CRP > 0 mg/L). Low-grade inflammation was significantly associated with female gender (p = 0.004), higher body mass index (p < 0.0001), current tobacco smoking (p < 0.0001), clomipramine (p = 0.04), quetiapine (p < 0.0001) and hypnotic (p = 0.0006) consumption while decreased hs-CRP blood levels was associated with aripiprazole (p = 0.004) and valproate/valpromide (p = 0.03) consumption. The present study suggests that some psychotropic drugs (quetiapine, cyamemazine, clomipramine) may be associated with increased peripheral low-grade inflammation in SZ patients while others (aripiprazole, valproate) may be associated with decreased peripheral low-grade inflammation. These results should be replicated in SZ and non-SZ populations and the biological underpinnings should be further explored.

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Acknowledgements

The FACE-SZ group: Andrianarisoa Md,l, Aouizerate Ba,l, MD PhD, Berna Fb,l, MD PhD, Blanc Oc,l, Msc, Brunel Ld,l, Msc, Bulzacka Ed,l, Msc, Capdevielle De,l, MD PhD, Chereau-Boudet Ic,l, MD, Chesnoy-Servanin Gf,l, Msc, Danion JMb,l, MD, D’Amato Tf,l, MD PhD, Deloge Ag,l, MD PhD, Delorme Ch,l, Msc, Denizot Hc,l, MD, Dorey JMf,l, MD, Dubertret Ci,l, MD PhD, Dubreucq Jh,l, MD, Faget Cj,l, MD, Fluttaz Ch,l, Msc, Fond Gd,l, MD, Fonteneau Sk,l, Msc, Gabayet Fh,l, Msc, Giraud-Baro Eh,l, MD, Hardy-Bayle MCk,l, MD PhD, Lacelle Dc,l, Msc, Lançon Cj,l, MD PhD, Laouamri Hl, Msc, Leboyer Md,l, MD PhD, Le Gloahec Td,l, Msc, Le Strat Yi,l, MD PhD, Llorcac,l PM, MD PhD, Mallet Ji,l, Metairie Ej,l, Msc, Misdrahi Dg,l, MD, Offerlin-Meyer Ib,l, PhD, Passerieux Ck,l, MD PhD, Peri Pj,l, Msc, Pires Sc,l, Msc, Portalier Ci,l, Msc, Rey Rf,l, MD, Roman Ch,l, Msc, Sebilleau Mk,l, Msc, Schandrin Ae,l, MD, Schürhoff Fd,l, MD PhD, Tessier Ag,l, Msc, Tronche AMc,l, MD, Urbach Mk,l, MD, Vaillant Fj,l, Msc, Vehier Af,l, Msc, Vidailhet Pb,l, MD PhD, Vilain Jd,l, MD, Vilà Eg,l, Msc, Yazbek He,l, PhD, Zinetti-Bertschy Ab,l, Msc.

aCentre Hospitalier Charles Perrens, F-33076 Bordeaux, France; Université de Bordeaux, Inserm, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France

bHôpitaux Universitaires de Strasbourg, Université de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France

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

dINSERM U955, équipe de psychiatrie translationnelle, Créteil, France, Université Paris-Est Créteil, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, Créteil, France

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

fINSERM 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

gCentre Hospitalier Charles Perrens, F-33076 Bordeaux, France; Université de Bordeaux, CNRS UMR 5287-INCIA

hCentre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France

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

jAssistance Publique des Hôpitaux de Marseille (AP-HM), pôle universitaire de psychiatrie, Marseille, France

kService de psychiatrie d’adulte, Centre Hospitalier de Versailles, Le Chesnay, EA 4047 HANDIReSP, UFR des Sciences de la Santé Simone Veil, Université Versailles Saint-Quentin en Yvelines, Versailles, France

lFondation Fondamental

This work was funded by AP-HP (Assistance Publique des Hôpitaux de Paris), 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, and by INSERM (Institut National de la Santé et de la Recherche Médicale).

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.

Author information

Authors and Affiliations

  1. Fondation FondaMental, Créteil, France

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

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

    G. Fond, F. Schürhoff, O. Godin, M. Andrianarisoa, L. Brunel, E. Bulzacka & M. Leboyer

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

    G. Fond, F. Schürhoff, O. Godin, M. Andrianarisoa, L. Brunel, E. Bulzacka & M. Leboyer

  4. Pôle psychiatrie universitaire, CHU Sainte-Marguerite, 13274, Marseille Cedex 09, France

    N. Resseguier & L. Boyer

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

    B. Aouizerate & D. Misdrahi

  6. Université de Bordeaux, 33000, Bordeaux, France

    B. Aouizerate & D. Misdrahi

  7. Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, 67000, Strasbourg, France

    F. Berna & P. Vidailhet

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

    D. Capdevielle & A. Schandrin

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

    I. Chereau & P. M. Llorca

  10. 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

  11. AP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, Inserm U894, Université Paris Diderot, Sorbonne Paris Cité, Faculté de médecine, 92700, Colombes, France

    C. Dubertret & J. Mallet

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

    J. Dubreucq & F. Gabayet

  13. Assistance Publique des Hôpitaux de Marseille (AP-HM), pôle universitaire de psychiatrie, Marseille, France

    C. Faget & C. Lançon

  14. 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

  15. Bordeaux Sleep Clinique, Pellegrin University Hospital, Bordeaux University, USR CNRS 3413 SANPSY, Research Unit, 33000, Bordeaux, France

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

  16. Inserm, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, 33000, Bordeaux, France

    B. Aouizerate

  17. CNRS, UMR 5287-INCIA, Bordeaux, France

    D. Misdrahi

  18. Pole de Psychiatrie, Hôpital A. Chenevier, 40 rue de Mesly, 94010, Créteil, France

    G. Fond

Authors
  1. G. Fond
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  2. N. Resseguier
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  3. F. Schürhoff
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  4. O. Godin
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  5. M. Andrianarisoa
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  6. L. Brunel
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  7. E. Bulzacka
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  8. B. Aouizerate
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  9. F. Berna
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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. F. Gabayet
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  17. C. Lançon
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  18. P. M. Llorca
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  19. J. Mallet
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  20. D. Misdrahi
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  21. C. Passerieux
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  22. R. Rey
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  23. A. Schandrin
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  24. M. Urbach
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  25. P. Vidailhet
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  26. L. Boyer
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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
  • , 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
  • , R. Rey
  • , C. Roman
  • , M. Sebilleau
  • , A. Schandrin
  • , F. Schürhoff
  • , A. Tessier
  • , A. M. Tronche
  • , M. Urbach
  • , F. Vaillant
  • , A. Vehier
  • , P. Vidailhet
  • , J. Vilain
  • , E. Vilà
  • , H. Yazbek
  •  & A. Zinetti-Bertschy

Corresponding author

Correspondence to G. Fond.

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Conflict of interest

The author(s) declare that they have no competing interests.

Additional information

The members of the the FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group are provided in the Acknowledgements section.

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Fond, G., Resseguier, N., Schürhoff, F. et al. Relationships between low-grade peripheral inflammation and psychotropic drugs in schizophrenia: results from the national FACE-SZ cohort. Eur Arch Psychiatry Clin Neurosci 268, 541–553 (2018). https://doi.org/10.1007/s00406-017-0847-1

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  • DOI: https://doi.org/10.1007/s00406-017-0847-1

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