Redefining peripheral inflammation signature in schizophrenia based on the real-world FACE-SZ cohort

Fond, Guillaume; Verville, P L Sunhary de; Richieri, Raphaëlle; Etchecopar‐Etchart, Damien; Korchia, Théo; Faugere, Mélanie; Godin, O.; Schürhoff, Franck; Berna, Fabrice; Aouizerate, Bruno; Capdevielle, Delphine; Chéreau, Isabelle; Clauss-Kobayashi, J.; Coulon, Nathalie; Dorey, Jean‐Michel; Dubertret, Caroline; Dubreucq, Julien; Mallet, J.; Misdrahi, D.; Passerieux, Christine; Pignon, Baptiste; Rey, Romain; Urbach, M.; Leboyer, Marion; Llorca, Pierre‐Michel; Lançon, Christophe; Boyer, Laurent

doi:10.1016/j.pnpbp.2021.110335

Cited by 5 publications

(4 citation statements)

References 41 publications

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“…2017; Orsolini et al, 2018;Momtazmanesh et al, 2019;Fond et al, 2021). Li et al demonstrated positive correlations between higher plasma IL-17 or TGF-β1 and severity of aggression in patients with ScZ (Li et al, 2016), however, we found slightly lower serum IL-17 and higher serum TGF-β1 in individuals with ScZ with aggression as compared with those without aggression.…”

Section: Discussioncontrasting

confidence: 67%

“…Crossing blood-brain barrier, the peripheral cytokines precipitate changes in mood and behavior through hypothalamic-pituitary-adrenal axis (Petra et al, 2015;Singh et al, 2019;Misiak et al, 2020), which lays a structural foundation for studying the involvement of inflammation in aggression. However, the mentioned cytokines except serum CRP are rarely profiled and potential sources of peripheral inflammation, with exception of being overweight or lack of dental care, are seldom explored (Fond et al, 2021) in individuals with aggression (Ag)-affected ScZ (ScZ-Ag).…”

Section: Introductionmentioning

confidence: 99%

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Bacterial Translocation Associates With Aggression in Schizophrenia Inpatients

Wang

Zhang

et al. 2021

Front. Syst. Neurosci.

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Objective: Accumulating evidence indicates that inflammation abnormalities may contribute to aggression behaviors in psychotic patients, however, the possible sources of inflammation remain elusive. We aimed to evaluate the associations among aggression, inflammation, and bacterial translocation (BT) in aggression-affected schizophrenia (ScZ) inpatients with 2 weeks of antipsychotics discontinuation.Methods: Serum specimens collected from 112 aggression and 112 non-aggression individuals with ScZ and 56 healthy adults were used for quantifications of inflammation- or BT-related biomarkers. Aggression severity was assessed by Modified Overt Aggression Scale (MOAS).Results: Proinflammation phenotype dominated and leaky gut-induced BT occurred only in cases with ScZ with a history of aggression, and the MOAS score positively related to levels of C-reactive protein, interleukin (IL)-6, IL-1β, and tumor necrosis factor-α. Furthermore, serum levels of BT-derived lipopolysaccharide (LPS), as well as LPS-responded soluble CD14, were not only positively correlated with levels of above proinflammation mediators but also the total MOAS score and subscore for aggression against objects or others.Conclusion: Our results collectively demonstrate the presence of leaky gut and further correlate BT-derived LPS and soluble CD14 to onset or severity of aggression possibly by driving proinflammation response in inpatients with ScZ, which indicates that BT may be a novel anti-inflammation therapeutic target for aggression prophylaxis.

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Section: Discussioncontrasting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Bacterial Translocation Associates With Aggression in Schizophrenia Inpatients

Wang

Zhang

et al. 2021

Front. Syst. Neurosci.

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“…6,48 However, while one could expect that poverty is associated with reduced quality of life in people with SSD, recent research from the FACE-SSD network has reported the opposite. 49 Apart from psychotic symptoms, depression was also found to contribute to the relationships between clinical and personal recovery. Depression affects on-third of people with SSD (35% in the present sample) and is known to impact negatively both physical and mental health.…”

Section: Overlap and Mutual Distinctions Between Clinical Recovery An...mentioning

confidence: 99%

Overlap and Mutual Distinctions Between Clinical Recovery and Personal Recovery in People With Schizophrenia in a One-Year Study

Dubreucq

Clauss-Kobayashi

Leigner

et al. 2021

Schizophrenia Bulletin

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Recovery is a multidimensional construct that can be defined either from a clinical perspective or from a consumer-focused one, as a self-broadening process aimed at living a meaningful life beyond mental illness. We aimed to longitudinally examine the overlap and mutual distinctions between clinical and personal recovery. Of 1239 people with schizophrenia consecutively recruited from the FondaMental Advanced Centers of Expertise for SZ network, the 507 present at one-year did not differ from those lost to follow-up. Clinical recovery was defined as the combination of clinical remission and functional remission. Personal recovery was defined as being in the rebuilding or in the growth stage of the Stages of Recovery Instrument (STORI). Full recovery was defined as the combination of clinical recovery and personal recovery. First, we examined the factors at baseline associated with each aspect of recovery. Then, we conducted multivariable models on the correlates of stable clinical recovery, stable personal recovery, and stable full recovery after one year. At baseline, clinical recovery and personal recovery were characterized by distinct patterns of outcome (i.e. better objective outcomes but no difference in subjective outcomes for clinical recovery, the opposite pattern for personal recovery, and better overall outcomes for full recovery). We found that clinical recovery and personal recovery predicted each other over time (baseline personal recovery for stable clinical recovery at one year; P = .026, OR = 4.94 [1.30–23.0]; baseline clinical recovery for stable personal recovery at one year; P = .016, OR = 3.64 [1.31–11.2]). In short, given the interaction but also the degree of difference between clinical recovery and personal recovery, psychosocial treatment should target, beyond clinical recovery, subjective aspects such as personal recovery and depression to reach full recovery.

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“…It has been described in previous studies that BMI and CRP levels are positive correlated in the general (non-psychiatric) population, as well as the schizophrenia patient population (Boozalis et al, 2019;Choi et al, 2013). Next to this, a recent study by Fond and colleagues presented that patients with a CRP level between 1 and 3 mg/L (which is considered as an indicator for peripheral inflammation) had a significantly higher BMI (Fond et al, 2021). By excluding people with high BMI (>30) from the prednisolone study, patients with higher CRP were most likely also excluded.…”

Section: Methodological Considerationsmentioning

confidence: 89%

Exploring opportunities for optimizing treatment in psychotic disorders

Nasib¹

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At present, treatment for psychotic disorder patients is suboptimal, as a substantial part of these patients do not sufficiently respond to currently available treatment options. In order to optimize treatment for these patients, there is a large need to explore how treatment can be improved. There are several options to optimize treatment for schizophrenia patients, of which two options are described in this dissertation: 1) novel augmentation therapies (i.e. anti-inflammatory drugs) and 2) improving currently available treatment by including schizophrenia patients with comorbidities in RCTs or by implementing precision medicine (i.e. TDM). In part I of this dissertation, no support for the beneficial effect of anti-inflammatory therapy in schizophrenia was found, which contradicts previous published meta-analyses, but is in line with the most recently published RCTs. It might be that treatment with statins or prednisolone is effective in a subgroup of patients in which low-grade inflammation in the central nerve system is present. Alternatively, it might be that mild anti-inflammatory drugs (e.g. aspirin) are more effective in a population with a high risk to develop psychosis (Ultra-high risk or Clinical High risk individuals), but this is yet to be determined. In part II of this dissertation two studies were presented with options to improve the application of currently available treatment. The first study of part II of this dissertation investigated the effect of excluding first-episode schizophrenia patients with comorbidities (such as suicidal ideation and/SUD). It was found that the exclusion of comorbidity patients did not have an impact on key RCT outcomes (symptomatic remission, premature study discontinuation, symptom severity and social performance) after four weeks of treatment with amisulpride. As first-episode schizophrenia patients with comorbidities are often excluded from efficacy trials, there is a gap in knowledge of the efficacy of antipsychotics in this group. As a result from this lack in knowledge, clinicians currently do not have an extensive scientific bases for treatment decisions in first episode schizophrenia patient.The second study of part II of this thesis examined whether an association could be found between amisulpride blood level and achieving symptomatic remission. Additionally, it was investigated whether there was an association between symptom severity (psychosis symptoms, depressive symptoms and severity of illness), mean dose and amisulpride blood level. It was also examined whether patient characteristics (age, sex, smoking, alchohol use and weight) had an effect on amisulpride blood level. The outcome of this study was that a low amisulpride blood level was significantly associated with a higher probability of going into symptomatic remission. Additionally, a lower blood level was associated with a better outcome; greater improvement in psychosis symptoms and severity of illness. With this study, no evidence was found for the implemention of TDM in amisulpride treatment, which is in contrast to the recommendation in the “Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology 2017” (Hiemke et al., 2017).

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Redefining peripheral inflammation signature in schizophrenia based on the real-world FACE-SZ cohort

Cited by 5 publications

References 41 publications

Bacterial Translocation Associates With Aggression in Schizophrenia Inpatients

Bacterial Translocation Associates With Aggression in Schizophrenia Inpatients

Overlap and Mutual Distinctions Between Clinical Recovery and Personal Recovery in People With Schizophrenia in a One-Year Study

Exploring opportunities for optimizing treatment in psychotic disorders

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