Lowered plasma paraoxonase (PON)1 activity is a trait marker of major depression and PON1 Q192R gene polymorphism-smoking interactions differentially predict the odds of major depression and bipolar disorder

Background: Major depression and bipolar disorder are accompanied by the activation of immune-inflammatory and Oxidative and Nitrosative Stress (O&NS) pathways and lowered levels of antioxidants. Paraoxonase (PON)1 (EC 3.1.8.1) is an antioxidant bound to High Density Lipoprotein (HDL). Polymorphisms in the PON1 Q192R coding sequence determine three functional genotypes, i.e. 192QQ, 192QR and 192RR.

Aims: This study was carried out to delineate the associations of plasma PON1 activity and functional PON1 Q192R genotypes in major depression and bipolar disorder.

Methods: PON1 status that is plasma PON1 abundance and three functional PON1 Q192R genotypes were assayed in 91 major depressed and 45 bipolar patients and compared to 199 normal controls.

Results: Major depression, but not bipolar disorder, was accompanied by lowered PON1 activity. PON1 activity was decreased by smoking and a diagnosis by genotype interaction (i.e. lower PON1 in major depression with the QQ genotype). Logistic regression showed that smoking by QQ genotype significantly increased the odds of bipolar disorder and that major depression was predicted by plasma PON1 activity, serum HDL cholesterol and interactions between genotype×smoking.

Discussion: The results suggest that lowered plasma PON1 activity is a trait marker of major depression and that PONQ192R gene-environment (smoking) interactions differentially predict the odds of depression and bipolar disorder.

Limitations: Association studies are prone to a risk of false positive findings and replication is essential.

Conclusions: The findings suggest that there are differential PON1 Q192R functional genotype×environment interactions in major depression and bipolar disorder. The effects of lowered PON1 activity may contribute to increased O&NS and immune-inflammatory burden in depression. PON1 status may contribute to the comorbidity between depression and other immune- and O&NS-related disorders, e.g. cardiovascular disorder.