Lowered paraoxonase 1 (PON1) activity is associated with increased cytokine levels in drug naive first episode psychosis

Background: Activated immune-inflammatory pathways play an important role in the pathophysiology of schizophrenia. Paraoxonase 1 (PON1) activity is inversely associated with inflammatory responses in numerous clinical conditions. The aims of this study were to delineate serum arylesterase PON1 activity in drug-naive first episode psychosis (PEP) patients and a healthy control group, and to assess whether there are inverse relationships between PON1 activity and cytokine levels. Methods: A total of 51 drug-naive FEP patients and 61 healthy controls were enrolled in this study. Levels of interleukin (IL)-4, IL-10, IL-6, tumor necrosis factor (TNF)-alpha and activity of PON1 were quantified. Results: Compared to healthy controls, FEP patients showed lower serum PON1 activity and higher levels of IL-4, IL-10 and TNF-alpha. A significant inverse relationship between PON1 activity and IL-4, IL-6 and IL-10 levels was detected, but not for TNF-alpha. Subjects with very low PON1 activity (25th quartile) presented significantly higher levels of IL-6, IL-10 and IL-4 than those with higher PON1 activity (75th quartile). Conclusion: The present study provides evidence that FEP is characterized by an inverse relationship between lowered activity of the anti-inflammatory/antioxidant enzyme PON1 and increased cytokine levels, including IL-6, IL-4 and IL-10 It is hypothesized that lowered PON1 activity may play a role in the immune-inflammatory response that accompanies PEP and that increased cytokine levels may further modulate PON1 activity. (C) 2015 Elsevier B.V. All rights reserved.