Baseline levels of C-reactive protein and proinflammatory cytokines are not associated with early response to amisulpride in patients with First Episode Psychosis: the OPTiMiSE cohort study

Susana Barbosa; Emanuela Martinuzzi; Iris E. C. Sommer; Paola Dazzan; Philip McGuire; Celso Arango; Covadonga M. Diaz-Caneja; W. Wolfgang Fleischhacker; D Rujescu; Birte Glenthøj; Inge Winter van Rossum; René Sylvain Kahn; Robert Yolken; Shôn W. Lewis; Richard Drake; Stefan Leucht; Cyprien Gilet; Olfa Khalfallah; Laetitia Davidovic; El Chérif Ibrahim; Raoul Belzeaux; Marion Leboyer; Nicolas Glaichenhaus

Baseline levels of C-reactive protein and proinflammatory cytokines are not associated with early response to amisulpride in patients with First Episode Psychosis: the OPTiMiSE cohort study

Susana Barbosa, Emanuela Martinuzzi, Iris E. C. Sommer, Paola Dazzan, Philip McGuire, Celso Arango, Covadonga M. Diaz-Caneja, W. Wolfgang Fleischhacker, D Rujescu, Birte Glenthøj, Inge Winter van Rossum, René Sylvain Kahn, Robert Yolken, Shôn W. Lewis, Richard Drake, Stefan Leucht, Cyprien Gilet, Olfa Khalfallah, Laetitia Davidovic, El Chérif IbrahimRaoul Belzeaux, Marion Leboyer, Nicolas Glaichenhaus

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Abstract

Background: Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammation
as demonstrated by elevated levels of C reactive protein (CRP) and pro-inflammatory
cytokines.
Aims: The primary goal of this study was to investigate the association between proinflammatory
biomarkers and clinical outcomes in unmedicated FEP patients.
Method: We used clinical data and biological samples from 289 FEP patients participating to
the Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE)
clinical trial. Patients were assessed at baseline and 4-5 weeks after treatment with
amisulpride. Baseline serum levels of interleukin (IL)-6, IL-8, Tumor Necrosis Factor (TNF)-α
and CRP were measured. We first used multivariable regression to investigate the association
between each of the four tested biomarkers and the following clinical outcomes: Positive And
Negative Syndrome Scale (PANSS), Calgary Depression Score for Schizophrenia (CDSS),
remission according to Andreasen’s criteria and Serious Adverse Events (SAEs). As a
complementary approach, we used an unsupervised clustering method to stratify patients into
an “inflamed” or a “non-inflamed” biotype based on baseline levels of IL-6, IL-8 and TNF-α. We
then used linear and logistic regressions to investigate the association between the patient
biotype and clinical outcomes.
Results: After adjusting for covariates and confounders, we did not find any association
between IL-6, IL-8, TNF-α, CRP or the patient biotype and clinical outcomes.
Implications: Our results do not support the existence of an association between baseline
levels of CRP and proinflammatory cytokines and early response to amisulpride in
unmedicated FEP patients.

Original language	English
Journal	Schizophrenia Bulletin Open
Publication status	Accepted/In press - 17 May 2021

Keywords

Inflammation, pro-inflammatory cytokines, remission, psychosis, longitudinal study

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Ms_Barbosa_SBO[1]Accepted author manuscript, 1.2 MB

Cite this

Barbosa, S., Martinuzzi, E., Sommer, I. E. C., Dazzan, P., McGuire, P., Arango, C., Diaz-Caneja, C. M., Wolfgang Fleischhacker, W., Rujescu, D., Glenthøj, B., van Rossum, I. W., Kahn, R. S., Yolken, R., Lewis, S. W., Drake, R., Leucht, S., Gilet, C., Khalfallah, O., Davidovic, L., ... Glaichenhaus, N. (Accepted/In press). Baseline levels of C-reactive protein and proinflammatory cytokines are not associated with early response to amisulpride in patients with First Episode Psychosis: the OPTiMiSE cohort study. Schizophrenia Bulletin Open.

@article{f42e52fe12444af9b705ab32a2ad0685,

title = "Baseline levels of C-reactive protein and proinflammatory cytokines are not associated with early response to amisulpride in patients with First Episode Psychosis: the OPTiMiSE cohort study",

abstract = "Background: Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammationas demonstrated by elevated levels of C reactive protein (CRP) and pro-inflammatorycytokines.Aims: The primary goal of this study was to investigate the association between proinflammatorybiomarkers and clinical outcomes in unmedicated FEP patients.Method: We used clinical data and biological samples from 289 FEP patients participating tothe Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE)clinical trial. Patients were assessed at baseline and 4-5 weeks after treatment withamisulpride. Baseline serum levels of interleukin (IL)-6, IL-8, Tumor Necrosis Factor (TNF)-αand CRP were measured. We first used multivariable regression to investigate the associationbetween each of the four tested biomarkers and the following clinical outcomes: Positive AndNegative Syndrome Scale (PANSS), Calgary Depression Score for Schizophrenia (CDSS),remission according to Andreasen{\textquoteright}s criteria and Serious Adverse Events (SAEs). As acomplementary approach, we used an unsupervised clustering method to stratify patients intoan “inflamed” or a “non-inflamed” biotype based on baseline levels of IL-6, IL-8 and TNF-α. Wethen used linear and logistic regressions to investigate the association between the patientbiotype and clinical outcomes.Results: After adjusting for covariates and confounders, we did not find any associationbetween IL-6, IL-8, TNF-α, CRP or the patient biotype and clinical outcomes.Implications: Our results do not support the existence of an association between baselinelevels of CRP and proinflammatory cytokines and early response to amisulpride inunmedicated FEP patients.",

keywords = "Inflammation, pro-inflammatory cytokines, remission, psychosis, longitudinal study",

author = "Susana Barbosa and Emanuela Martinuzzi and Sommer, {Iris E. C.} and Paola Dazzan and Philip McGuire and Celso Arango and Diaz-Caneja, {Covadonga M.} and {Wolfgang Fleischhacker}, W. and D Rujescu and Birte Glenth{\o}j and {van Rossum}, {Inge Winter} and Kahn, {Ren{\'e} Sylvain} and Robert Yolken and Lewis, {Sh{\^o}n W.} and Richard Drake and Stefan Leucht and Cyprien Gilet and Olfa Khalfallah and Laetitia Davidovic and Ibrahim, {El Ch{\'e}rif} and Raoul Belzeaux and Marion Leboyer and Nicolas Glaichenhaus",

year = "2021",

month = may,

day = "17",

language = "English",

journal = "Schizophrenia Bulletin Open",

issn = "2632-7899",

publisher = "Oxford University Press (OUP)",

}

Barbosa, S, Martinuzzi, E, Sommer, IEC, Dazzan, P , McGuire, P, Arango, C, Diaz-Caneja, CM, Wolfgang Fleischhacker, W, Rujescu, D, Glenthøj, B, van Rossum, IW, Kahn, RS, Yolken, R, Lewis, SW, Drake, R, Leucht, S, Gilet, C, Khalfallah, O, Davidovic, L, Ibrahim, EC, Belzeaux, R, Leboyer, M & Glaichenhaus, N 2021, 'Baseline levels of C-reactive protein and proinflammatory cytokines are not associated with early response to amisulpride in patients with First Episode Psychosis: the OPTiMiSE cohort study', Schizophrenia Bulletin Open.

Baseline levels of C-reactive protein and proinflammatory cytokines are not associated with early response to amisulpride in patients with First Episode Psychosis: the OPTiMiSE cohort study. / Barbosa, Susana; Martinuzzi, Emanuela; Sommer, Iris E. C. et al.
In: Schizophrenia Bulletin Open, 17.05.2021.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Baseline levels of C-reactive protein and proinflammatory cytokines are not associated with early response to amisulpride in patients with First Episode Psychosis: the OPTiMiSE cohort study

AU - Barbosa, Susana

AU - Martinuzzi, Emanuela

AU - Sommer, Iris E. C.

AU - Dazzan, Paola

AU - McGuire, Philip

AU - Arango, Celso

AU - Diaz-Caneja, Covadonga M.

AU - Wolfgang Fleischhacker, W.

AU - Rujescu, D

AU - Glenthøj, Birte

AU - van Rossum, Inge Winter

AU - Kahn, René Sylvain

AU - Yolken, Robert

AU - Lewis, Shôn W.

AU - Drake, Richard

AU - Leucht, Stefan

AU - Gilet, Cyprien

AU - Khalfallah, Olfa

AU - Davidovic, Laetitia

AU - Ibrahim, El Chérif

AU - Belzeaux, Raoul

AU - Leboyer, Marion

AU - Glaichenhaus, Nicolas

PY - 2021/5/17

Y1 - 2021/5/17

N2 - Background: Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammationas demonstrated by elevated levels of C reactive protein (CRP) and pro-inflammatorycytokines.Aims: The primary goal of this study was to investigate the association between proinflammatorybiomarkers and clinical outcomes in unmedicated FEP patients.Method: We used clinical data and biological samples from 289 FEP patients participating tothe Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE)clinical trial. Patients were assessed at baseline and 4-5 weeks after treatment withamisulpride. Baseline serum levels of interleukin (IL)-6, IL-8, Tumor Necrosis Factor (TNF)-αand CRP were measured. We first used multivariable regression to investigate the associationbetween each of the four tested biomarkers and the following clinical outcomes: Positive AndNegative Syndrome Scale (PANSS), Calgary Depression Score for Schizophrenia (CDSS),remission according to Andreasen’s criteria and Serious Adverse Events (SAEs). As acomplementary approach, we used an unsupervised clustering method to stratify patients intoan “inflamed” or a “non-inflamed” biotype based on baseline levels of IL-6, IL-8 and TNF-α. Wethen used linear and logistic regressions to investigate the association between the patientbiotype and clinical outcomes.Results: After adjusting for covariates and confounders, we did not find any associationbetween IL-6, IL-8, TNF-α, CRP or the patient biotype and clinical outcomes.Implications: Our results do not support the existence of an association between baselinelevels of CRP and proinflammatory cytokines and early response to amisulpride inunmedicated FEP patients.

AB - Background: Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammationas demonstrated by elevated levels of C reactive protein (CRP) and pro-inflammatorycytokines.Aims: The primary goal of this study was to investigate the association between proinflammatorybiomarkers and clinical outcomes in unmedicated FEP patients.Method: We used clinical data and biological samples from 289 FEP patients participating tothe Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE)clinical trial. Patients were assessed at baseline and 4-5 weeks after treatment withamisulpride. Baseline serum levels of interleukin (IL)-6, IL-8, Tumor Necrosis Factor (TNF)-αand CRP were measured. We first used multivariable regression to investigate the associationbetween each of the four tested biomarkers and the following clinical outcomes: Positive AndNegative Syndrome Scale (PANSS), Calgary Depression Score for Schizophrenia (CDSS),remission according to Andreasen’s criteria and Serious Adverse Events (SAEs). As acomplementary approach, we used an unsupervised clustering method to stratify patients intoan “inflamed” or a “non-inflamed” biotype based on baseline levels of IL-6, IL-8 and TNF-α. Wethen used linear and logistic regressions to investigate the association between the patientbiotype and clinical outcomes.Results: After adjusting for covariates and confounders, we did not find any associationbetween IL-6, IL-8, TNF-α, CRP or the patient biotype and clinical outcomes.Implications: Our results do not support the existence of an association between baselinelevels of CRP and proinflammatory cytokines and early response to amisulpride inunmedicated FEP patients.

KW - Inflammation, pro-inflammatory cytokines, remission, psychosis, longitudinal study

M3 - Article

SN - 2632-7899

JO - Schizophrenia Bulletin Open

JF - Schizophrenia Bulletin Open

ER -

Baseline levels of C-reactive protein and proinflammatory cytokines are not associated with early response to amisulpride in patients with First Episode Psychosis: the OPTiMiSE cohort study

Abstract

Keywords

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