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Eur Arch Psychiatry Clin Neurosci. 2018 Sep;268(6):541-553. doi: 10.1007/s00406-017-0847-1. Epub 2017 Nov 10.

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

Fond G1,2,3,4,5, Resseguier N6,7,8, Schürhoff F6,9,10,8, Godin O6,9,10,8, Andrianarisoa M6,9,10,8, Brunel L6,9,10,8, Bulzacka E6,9,10,8, Aouizerate B6,11,12,8,13, Berna F6,14,8, Capdevielle D6,15,8, Chereau I6,16,8, D'Amato T6,17,8, Dubertret C6,18,8, Dubreucq J6,19,8, Faget C6,20,8, Gabayet F6,19,8, Lançon C6,20,8, Llorca PM6,16,8, Mallet J6,18,8, Misdrahi D6,11,12,8,21, Passerieux C6,22,8, Rey R6,17,8, Schandrin A6,15,8, Urbach M6,22,8, Vidailhet P14,8, Boyer L6,7,8, Leboyer M6,9,10,8; FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group.

Author information

Fondation FondaMental, Créteil, France.
INSERM U955, équipe de psychiatrie translationnelle, Créteil, France.
Université Paris-Est Créteil, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, Créteil, France.
Bordeaux Sleep Clinique, Pellegrin University Hospital, Bordeaux University, USR CNRS 3413 SANPSY, Research Unit, 33000, Bordeaux, France.
Pole de Psychiatrie, Hôpital A. Chenevier, 40 rue de Mesly, 94010, Créteil, France.
Fondation FondaMental, Créteil, France.
Pôle psychiatrie universitaire, CHU Sainte-Marguerite, 13274, Marseille Cedex 09, France.
Bordeaux Sleep Clinique, Pellegrin University Hospital, Bordeaux University, USR CNRS 3413 SANPSY, Research Unit, 33000, Bordeaux, France.
INSERM U955, équipe de psychiatrie translationnelle, Créteil, France.
Université Paris-Est Créteil, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, Créteil, France.
Centre Hospitalier Charles Perrens, 33076, Bordeaux, France.
Université de Bordeaux, 33000, Bordeaux, France.
Inserm, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, 33000, Bordeaux, France.
Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, 67000, Strasbourg, France.
Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France.
CMP B, CHU, EA 7280 Faculté de Médecine, Université d'Auvergne, BP 69, 63003, Clermont-Ferrand Cedex 1, France.
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.
AP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, Inserm U894, Université Paris Diderot, Sorbonne Paris Cité, Faculté de médecine, 92700, Colombes, France.
Centre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France.
Assistance Publique des Hôpitaux de Marseille (AP-HM), pôle universitaire de psychiatrie, Marseille, France.
CNRS, UMR 5287-INCIA, Bordeaux, France.
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.


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.


Antidepressant; Antipsychotic; Inflammation; Schizophrenia; Valproate

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