Evaluation of serum paraoxonase levels in patients with major depressive disorder

Objective: Major Depressive Disorder is known to involve increased oxidative stress and impaired antioxidant defense mechanisms. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)–associated antioxidant enzyme and an important marker of oxidative stress biology. The aim of this study was to compare serum PON1 activity between patients with majör depressive disorder and healthy controls and to examine its relationship with clinical subtypes of depression. Methods: This case–control study included 64 patients diagnosed with majör depressive disorder according to DSM-5 criteria and 64 healthy controls. Serum PON1 activity was measured using a spectrophotometric method. Depression severity was assessed using the Hamilton Depression Rating Scale (HAM-D) and the Depression Anxiety Stress Scale-21 (DASS-21). First-episode and recurrent depression subgroups were compared. Appropriate parametric and non-parametric tests were used for group comparisons, and receiver operating characteristic (ROC) analysis was performed to evaluate the discriminative ability of PON1 for majör depressive disorder. Results: In the major depressive disorder group, serum PON1 activity was found to be significantly lower compared with the healthy control group (129.3 U/L vs. 170.6 U/L; p < 0.001). No statistically significant differences were observed between the patient and control groups with respect to age, sex, or smoking status. PON1 levels were lower in the first-episode depression group compared with the recurrent depression group; however, PON1 levels in both patient groups remained below those of healthy individuals. No statistically significant associations were detected between PON1 activity and HAM-D or DASS-21 subscale scores. ROC analysis demonstrated that serum PON1 activity had a statistically significant ability to discriminate individuals with major depressive disorder from healthy controls (AUC = 0.706). At the cut-off value of 97.5 determined by the Youden index, sensitivity was 50.0% and specificity was 89.1%. VIII Conclusion: The marked reduction in serum PON1 activity in major depressive disorder suggests that disturbances in the oxidative stress–antioxidant balance may be associated with biological processes accompanying the illness. The observation of lower PON1 levels in first-episode depression indicates that these biological processes may be more pronounced in the early stages of the disorder. However, the absence of a direct association between PON1 levels and symptom severity suggests that this enzyme may reflect the biological presence of the disorder rather than its clinical severity. Findings from the ROC analysis indicate that, owing to its high specificity, PON1 demonstrates strength in correctly identifying healthy individuals, whereas its relatively low sensitivity may limit its ability to detect all depressive cases. Accordingly, PON1 may be more appropriately considered as a supportive parameter within multimarker approaches rather than as a standalone diagnostic tool. Keywords: Major depressive disorder, paraoxonase-1, oxidative stress, biomarker, first-episode depression.