Lowered PON1 activities are strongly associated with depression and bipolar disorder, recurrence of (hypo)mania and depression, increased disability and lowered quality of life.

Background: Mood disorders (MD) frequently co-exist with cardiovascular disease (CVD) and immune-inflammatory and oxidative stress are important shared pathophysiological pathways. Even though there is an extensive investigation of the enzyme paraoxonase 1 (PON1) as a biomarker of susceptibility for CVD, there are only few reports studying PON1 in MD. Objectives: To determine the association between PON1 activities as well as functional genotypes and MD diagnosis, clinical characteristics and outcomes. Methods: PON1 activities and functional genotypes were assayed in 58 bipolar (BD) and 32 major depressed patients (MDD) and compared to 59 controls. Results: Our findings show significantly lower PON1 total and CMPAase activities in MD, which are partly related to the number of previous depressive and manic episodes. Lowered CMPAase activity is associated with a worse outcome of MD as indicated by lowered quality of life (WHOQoL-BREF scale) and increased disability in the Sheeham scale. Conclusions: We hypothesize that lowered PON1 total and CMPAase activities may play a role in the pathophysiology of MD by lowering antioxidant defences thereby increasing the risk towards lipid peroxidation and inflammation; lowered inhibition of quorum sensing lactones thereby increasing bacterial proliferation; and attenuated homocysteine thiolactone catabolism which may trigger immune-inflammatory response and/or induce neurotoxicity.