Investigation of the relationship between obsessive-compulsive disorder and NLRP3 inflammasome activity

Introduction: In the studies performed in patients with obsessive-compulsive disorder (OCD) and in healthy controls, the levels of the major pro-inflammatory and anti-inflammatory cytokines in the blood were examined and clues were obtained that suggested neuroinflammatory irregularities. However, the role of inflammation in the pathogenesis of OCD is controversial. Aim and Hypothesis: The aim of this study was to determine the possible role of NLRP3 inflammasome in the inflammatory processes that are thought to play a role in OCD pathophysiology and to evaluate its relationship with clinical features. The hypothesis of this study is that inflammation in OCD, which is thought to play a role in its etiology, is effective through NLRP3 inflammasome. Methods: The study included 51 patients aged between 18-45 years who were diagnosed with OCD according to DSM-IV, and 52 healthy age and gender matched controls with no history of psychiatric disease. "Structured Clinical Interview", "Yale Brown Obsession and Compulsion Scale", "Hamilton Depression Scale" and "Hewitt Perfectionism Scale" were applied to all participants. RNA and protein were extracted from the peripheral blood mononuclear cells (PKMH) isolated from patients and control blood samples. mRNA and protein expression levels of the NLRP3 inflammasome components NLRP3, Kaspaz-1 and ASC genes, as well as that of NEK7 gene, which regulate the activity of NLRP3, was determined by quantitative real-time PCR (qRT-PCR) and Western blotting methods, respectively. Serum IL-1beta and IL-18 cytokine levels were determined by ELISA method. Results: NEK7 and Kaspaz-1 mRNA expression levels were higher in OCD patients compared to healthy controls. Regression analysis suggested that, NEK7 mRNA expression level can discriminate patient and healthy groups. When the relationship between inflammasome subunits and OCD subgroups was examined, ASC mRNA level was correlated with religious-sexual obsession-compulsion subgroup of OCD. Conclusion: NEK7 and Kaspaz-1 gene expression levels in the blood can be used as biomarkers in OCD, and may help explain inflammatory changes in OCD. Keywords: Obsessive compulsive disorder, NLRP3, İnflammasome, Kaspaz-1, ASC, NEK7 genes