Increased NLRP3 inflammasome expression in peripheral blood mononuclear cells of patients with schizophrenia: a case-control study

Abstract

Objective

This study aimed to evaluate the gene expression of the P2X purinoceptor 7 (P2X7R)- nod-like receptor pyrin domain-containing protein 3 (NLRP3) signal pathway in peripheral blood mononuclear cells (PBMCs) between schizophrenia (SCZ) patients and healthy controls (HC) to reveal its relationship with clinical variables.

Methods

Thirty-two SCZ patients and 41 healthy controls were included in this study. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS), The Global Assessment of Functioning (GAF) scale and the Functioning Assessment Short Test (FAST) scales were applied. P2X7R, NLRP3, IL-1β and IL-18 gene expression levels were evaluated by real-time polymerase chain reaction in PBMCs.

Results

NLRP3, P2RX7, IL-1β and IL-18 expression levels were significantly higher in PBMCs of SCZ patients than in HC subjects. Negative correlations were found between NLRP3 gene expression levels and GAF and FAST scales scores. There was a negative correlation between IL-18 expression levels and the GAF and FAST scales scores and a positive correlation with the SAPS scale scores.

Conclusions

Systemic inflammation is implicated in SCZ pathogenesis, according to our findings, which suggest that the NLRP3 pathway may be involved. The NLRP3 inflammasome may serve as a biomarker for SCZ, and its pharmacological regulation may be a promising treatment approach.

Key points

• We hypothesised that the NLRP3 pathway may contribute to the etiopathogenesis of schizophrenia.

• NLRP3, IL-1β and IL-18 mRNA levels were higher in patients with schizophrenia compared to healthy controls.

• Negative correlations were found between NLRP3 gene expression levels and GAF and FAST scales scores.

• There was a negative correlation between IL-18 expression levels and the GAF and FAST scales scores.

• The SAPS scale scores and IL-18 expression levels had a positive correlation.

• Given all these findings, it can be stated that NLRP3 inflammasome may play a role in the pathogenesis and symptoms of schizophrenia.

Keywords:

• Schizophrenia
• NLRP3
• P2X7R
• inflammasome
• IL-1β
• IL-18

Acknowledgements

The authors thank all patients and controls for participating in this study. They have no financial disclosure to declare. Preliminary data of this study were accepted as an oral presentation to be presented at the 25th National Social Psychiatry Congress (25 May 2022, Ankara, Turkey, online).

Disclosure statement

No potential conflict of interest was reported by the author(s).