Abstract
BACKGROUND: Oxidative stress is increasingly implicated in the pathophysiology of major depressive disorder (MDD), which is often accompanied by significant cognitive impairments. However, the interplay between oxidative stress markers, cognitive function, and the severity of depression symptom, particularly the potential mediating role of severity, requires further investigation. This study aimed to examine alterations in oxidative stress markers in Chinese patients with MDD, their association with cognitive performance, and whether depression and anxiety severity mediates this relationship. METHODS: Forty-four patients meeting DSM-5 criteria for MDD and 47 matched healthy controls (CON) were recruited. Cognitive functions were assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test. Depression and anxiety severity were evaluated using the Hamilton Depression Rating Scale (HAMD-24) and Hamilton Anxiety Rating Scale (HAMA). Plasma levels of oxidative stress markers, including malondialdehyde (MDA) and catalase (CAT), were measured via ELISA. Group comparisons (controlling for education), correlation analyses, and mediation analyses (using bootstrapping) were performed. RESULTS: Compared to healthy controls, patients with MDD exhibited significantly higher plasma MDA levels (1.9 ± 0.4 vs. 1.6 ± 0.5 nmol/mL, P = 0.025) and lower CAT activity (0.7 ± 0.2 vs. 0.9 ± 0.3 U/mL, P = 0.020). The MDD group showed significant cognitive deficits in immediate memory (P = 0.002), attention (P < 0.001), delayed memory (P = 0.010), and the RBANS total score (P = 0.002). Plasma MDA levels negatively correlated with immediate memory (r = - 0.34, P = 0.033) and delayed memory (r = - 0.36, P = 0.021), and positively correlated with both HAMD (P = 0.041) and HAMA scores (P = 0.048). Mediation analyses revealed that HAMD and HAMA scores significantly mediated the relationship between plasma MDA levels and immediate memory performance (Indirect effect P < 0.05 for both). CONCLUSIONS: Chinese patients with MDD demonstrate heightened oxidative stress (elevated MDA, reduced CAT) and impaired cognitive function, particularly in memory domains, compared to healthy individuals. Higher levels of oxidative stress marker MDA are associated with greater depression/anxiety severity and poorer memory performance. Furthermore, symptom severity partially mediates the link between oxidative stress and immediate memory deficits, suggesting a complex interplay among these factors in MDD pathophysiology.