Blood Levels of NLRP3 Inflammasome Components is Associated with Obsessive Compulsive Disorder

Abstract

Background: Inflammation has a well-known role in the pathogenesis of a range of neuropsychiatric disorders such as major depressive disorder and schizophrenia. Previous studies provided evidence regarding its possible involvement in the etiology of obsessive-compulsive disorder (OCD). However, mechanisms explaining the association of inflammation with OCD are lacking. The NLRP3 inflammasome complex initiates and mediates inflammatory response, which explain one of the most important key mechanisms behind inflammatory response. In this study, we aimed to determine a possible association between NLRP3 inflammasome and OCD, and to evaluate its relationship with clinical features. Methods: This case-control study included 103 participants (51 OCD and 52 healthy controls). OCD patients were diagnosed using DSM-IV criteria. All participants were evaluated by psychiatric inventories, i.e. Yale Brown Obsessive Compulsive Scale, Hamilton Depression Scale, and Hewitt Multidimensional Perfectionism Scale. Peripheral blood mononuclear cells (PBMCs) were isolated from fresh blood samples. RNA and protein were extracted from PBMCs and expression of NLRP3 inflammasome components were evaluated by quantitative real-time PCR (qPCR) and Western blotting. Serum IL-1beta and IL-18 cytokine levels were determined by ELISA. Results: NEK7 and CASP1 mRNA levels were significantly higher in OCD patients, compared to controls. Pro-Caspase-1 protein levels were elevated, as well. Regression analysis showed that NEK7 mRNA and Caspase-1 protein levels can differentiate OCD and healthy control groups. Discussion: pro-Caspase-1 mRNA and protein levels in PBMCs, as well as NEK7 mRNA levels are potential biomarker candidates in OCD. Our results may prompt research into possible role of NLRP3 inflammasome in OCD etiology.