Abstract
Introduction: The etiology of generalized anxiety disorder (GAD) has not been fully understood, and oxidative stress may potentially contribute to its pathogenesis. However, there is no published evidence concerning the possible influence of oxidative stress on antidepressant treatment outcomes. This study investigated the ability of oxidative stress markers to predict treatment outcomes in GAD patients treated with selective serotonin reuptake inhibitors (SSRIs). Methods: One hundred-one GAD patients and 100 healthy controls (HCs) were included in this study. The 101 GAD patients were selected for treatment with escitalopram (n = 52) or sertraline (n = 49) for 8 weeks. Hamilton Anxiety Rating Scale (HAM-A) assessments were conducted before and after treatment. The serum levels of eight oxidative stress makers, malondialdehyde (MDA), lipid hydroperoxides (LPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), cortisol, high-density lipoprotein (HDL), and nitric oxide (NO) were measured using enzyme-linked immunosorbent assays (ELISA) before and after SSRI treatment in GAD patients and at the time of HC enrollment. Results: The serum levels of MDA, cortisol, and LPO were higher in GAD patients than in HCs (all p < 0.001), while SOD, GSH-Px, and CAT were lower than in HCs (all p < 0.001). The baseline MDA, LPO, NO, and cortisol levels were positively correlated with anxiety severity, while GSH-Px was negatively correlated. After 8 weeks of SSRI treatment, the GSH-Px levels increased, and MDA and LPO decreased (all p < 0.05). Alterations in MDA levels covaried with changes in anxiety measures (all p < 0.05). The ability of the receiver-operating characteristic (ROC) area of the baseline MDA levels to predict the SSRI endpoint treatment response was 0.804 (p < 0.05). Conclusion: The pathogenesis of GAD might involve oxidative stress. Moreover, serum MDA levels might predict treatment response to SSRIs. However, more research is warranted to confirm these findings.
Plain Language Summary
Among anxiety disorders, GAD is a chronic mental disorder characterized by persistent, excessive anxiety. Previous studies indicate that oxidative stress plays an important role in the pathophysiology of GAD. So far, there is no evidence that SSRI treatment alters the level of oxidative stress in GAD patients and whether oxidative stress biomarkers can predict treatment response to SSRIs. To clarify these issues, we aimed to investigate oxidative stress markers associated with GAD, including malondialdehyde (MDA), lipid hydroperoxides (LPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), cortisol, HDL, and NO, to address the following five questions: (1) compare the levels of these eight oxidative stress markers between GAD patients and HCs; (2) investigate potential correlations between the baseline levels of oxidative stress markers in GAD patients and HAM-A scores; (3) examine whether SSRI treatment affects the oxidative stress marker levels in GAD patients compared with before treatment; (4) determine whether oxidative stress marker changes were associated with improvements in anxiety symptoms; and (5) identify whether baseline oxidative stress markers predicted the treatment response to SSRIs. The current study provides new evidence concerning on oxidative stress being involved in the pathophysiology of GAD. Oxidative stress marker levels correlated with symptom severity of GAD. MDA and LPO are downregulated, and GSH-Px was elevated after SSRI administration. The observed changes were associated with improved anxiety symptoms. The study also demonstrated that a decreased MDA level at baseline could predict the treatment response to SSRIs.
