Inflammation in psychosis: A potential role for Toll-like receptors

Schizophrenia is a psychiatric disorder with complex aetiology. There has been a growing interest in the role of Toll-like receptors (TLRs) and cytokines in the pathophysiology of schizophrenia. TLRs are pattern recognition receptors involved in immune mediation. We aim to investigate if there is al...

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Bibliographic Details
Published in:Psychoneuroendocrinology Vol. 160; p. 106737
Main Authors: McKernan, Declan, Patlola, Saahithh Reddi, Laighneach, Aodhán, Corley, Emma, King, Sinéad, Holleran, Laurena, Kelly, John P., Morris, Derek, McDonald, Colm, Donohoe, Gary
Format: Journal Article
Language:English
Published: Elsevier Ltd 01-02-2024
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Summary:Schizophrenia is a psychiatric disorder with complex aetiology. There has been a growing interest in the role of Toll-like receptors (TLRs) and cytokines in the pathophysiology of schizophrenia. TLRs are pattern recognition receptors involved in immune mediation. We aim to investigate if there is altered expression and activity of peripheral cytokines and TLRs in patients with schizophrenia. 279 participants were included in this study. We used high-sensitive ELISA kits to detect peripheral levels of cytokines in the plasma of both healthy volunteers (N=189) and patients with schizophrenia (N=90). Whole-blood was stimulated with TLR2-4 agonists to investigate cytokine activity. cDNA synthesised from purified mRNA was used to perform qRT-PCR to analyse the relative expression of cytokines and TLRs. Data from ELISAs show significantly elevated levels of IL-6, IL-8, IL-10, TNF-a and CRP (p<0.01) but not IL- 12 and IFN-g in patients with schizophrenia compared to controls. Significant higher levels of IL-6 and IL-8 in patients were observed post TLR2 and TLR4 receptor stimulation. The mRNA expression analysis illustrated a significant higher expression of IL-6 (1.3-fold, p<0.06) and IL-8 (1.44-fold, p<0.001) and not with TNF-a. A significant upregulation in the mRNA expression of TLR2 (1.1-fold, p<0.05) and TLR4 (1.3-fold, p<0.01) was observed but not with TLR3. These results suggest that patients with schizophrenia show altered inflammatory activity. They also point in the direction of possible role of Toll-like receptors in the mediation of neuroinflammatory response in schizophrenia.
ISSN:0306-4530
1873-3360
DOI:10.1016/j.psyneuen.2023.106737