Expression and Functionality Study of 9 Toll-Like Receptors in 33 Drug-Naïve Non-Affective First Episode Psychosis Individuals: A 3-Month Study

Toll-like receptors (TLRs) are a pivotal component of the innate immune system that seem to have a role in the pathogenesis of psychosis. The purpose of this work was to compare the expression and functionality of 9 TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells, and T cells) between 33 drug-naïve first-episode psychosis (FEP) individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment. The expression of TLRs 1–9 were assessed by flow cytometry. For the assessment of the TLR functionality, cells collected in sodium heparin tubes were polyclonally stimulated for 18 h, with different agonists for human TLR1–9. The results of our study highlight the role that TLR5 and TLR8 might play in the pathophysiology of psychosis. We found a lower expression of these receptors in FEP individuals, regarding healthy volunteers at baseline and after 3-month of treatment on the three PBMCs subsets. Most TLRs showed a lower functionality (especially reduced intracellular levels of TNF-α) in patients than in healthy volunteers. These results, together with previous evidence, suggest that individuals with psychosis might show a pattern of TLR expression that differs from that of healthy volunteers, which could vary according to the intensity of immune/inflammatory response.

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Expression and functionality study of 9 Toll-like receptors in drug-naïve non-affective first episode psychosis individuals: a 3-month study

10.21203/rs.3.rs-17979/v1 ◽

2020 ◽

Author(s):

Maria Juncal-Ruiz ◽

Laura Riesco-Davila ◽

Mariluz Ramirez-Bonilla ◽

Victor Ortiz-Garcia de la Foz ◽

Javier Vazquez-Bourgon ◽

...

Keyword(s):

Healthy Volunteers ◽

Inflammatory Cytokines ◽

Mononuclear Cells ◽

Immune Cell ◽

First Episode ◽

Toll Like Receptors ◽

Tnf Α ◽

Drug Naïve ◽

Lower Expression ◽

Pro Inflammatory Cytokines

Abstract Background: Toll-like receptors (TLRs) are a pivotal component of the innate immune system, which are expressed by various subsets of immune cell types, included central nervous system. There are few publications that have studied TLR expression and/or functionality in psychosis, of which most of them have been based on chronic schizophrenia individuals.Objectives: To compare the expression and functionality of 9TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells and T cells) within a sample of 33 drug-naïve FEP individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment.Methods: The expression of TLR1-9 was assessed by ﬂow cytometry. For the assessment of the TLR functionality (measured as intracellular production of IL-1β, IL-6 and TNF-α following TLR stimulation), cells collected in sodium heparin tubes were polyclonally stimulated for 18h with different agonists for human TLR1–9.Results: Patients showed a lower expression of TLR5 and TLR8 on the three PBMCs at baseline and after 3-month of treatment regarding healthy volunteers (all ps <0.01). We also found less production of some intracellular pro-inflammatory cytokines (especially TNF-α) after TLR stimulation in patients at both baseline and following the medication (all ps <0.01). We have not found differences in the intra-subject analyses after 3-month of treatment.Conclusions: Drug-naive patients with schizophrenia spectrum disorders show lower expression of specific TLR receptors as well as lower intracellular concentrations of some pro-inflammatory cytokines after TLR stimulation. These findings may be a consequence of an excessive cell stimulation via exogenous ligands (such as pathogens) and/or endogenous ligands (such as autoimmunity) in such a way that PBMCs could be exhausted to be activated in the in vitro analyses.

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Specificity proteins 1 and 4, hippocampal volume and first-episode psychosis

The British Journal of Psychiatry ◽

10.1192/bjp.bp.114.152140 ◽

2016 ◽

Vol 208 (6) ◽

pp. 591-592 ◽

Cited By ~ 1

Author(s):

Montserrat Fusté ◽

Iria Meléndez-Pérez ◽

Victoria Villalta-Gil ◽

Raquel Pinacho ◽

Núria Villalmanzo ◽

...

Keyword(s):

Mononuclear Cells ◽

Hippocampal Volume ◽

First Episode Psychosis ◽

Magnetic Resonance Images ◽

First Episode ◽

Peripheral Blood Mononuclear ◽

Specificity Protein 1 ◽

Episode Psychosis ◽

Morphometry Analysis ◽

Specificity Protein

SummaryWe assessed specificity protein 1 (SP1) and 4 (SP4) transcription factor levels in peripheral blood mononuclear cells and conducted a voxel-based morphometry analysis on brain structural magnetic resonance images from 11 patients with first-episode psychosis and 14 healthy controls. We found lower SP1 and SP4 levels in patients, which correlated positively with right hippocampal volume. These results extend previous evidence showing that such transcription factors may constitute a molecular pathway to the development of psychosis.

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A Meta-Analysis of the Influence of Antipsychotics on Cytokines Levels in First Episode Psychosis

Journal of Clinical Medicine ◽

10.3390/jcm10112488 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2488

Author(s):

Piotr Marcinowicz ◽

Magdalena Więdłocha ◽

Natalia Zborowska ◽

Weronika Dębowska ◽

Piotr Podwalski ◽

...

Keyword(s):

Meta Analysis ◽

First Episode Psychosis ◽

First Episode ◽

Antipsychotic Treatment ◽

Episode Psychosis ◽

Tnf Α ◽

Before And After ◽

Ifn Γ ◽

Anti Inflammatory ◽

Meta Analyses

Background: Cytokines have a major impact on the neurotransmitter networks that are involved in schizophrenia pathophysiology. First Episode Psychosis (FEP) patients exhibit abnormalities in cytokines levels prior to the start of treatment. Previous studies showed that antipsychotic treatment modulates cytokines levels. The aim of this meta-analysis is to further investigate this relationship. Methods: Several online databases were searched. For meta-analysis of selected studies, we analysed variables containing the number of cases, mean and standard deviation of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFN-γ levels before, and after, antipsychotic treatment. Results: 12 studies were included in the meta-analysis. Our main results demonstrate that, in FEP patients, antipsychotic treatment is related to decreased concentrations of pro-inflammatory IL-1β, IL-6, IFN-γ, TNF-α and anti-inflammatory IL-4, IL-10 cytokines. On the other hand, levels of pro-inflammatory IL-2 and IL-17 remain unaffected. Conclusions: When compared with other meta-analyses of studies involving FEP individuals, results we obtained are consistent regarding decrease in IL-1β, IL-6. Comparing outcomes of our study with meta-analyses of schizophrenic subjects, in general, our results are consistent in IL-1β, IL-6, TNF-α, IFN-γ, IL-2. Our meta-analysis is the only one which indicates a decrease in anti-inflammatory IL-10 in FEP patients after antipsychotic treatment.

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