Plasma oxidative stress marker levels related to functional brain abnormalities in first-episode drug-naive major depressive disorder

Major Depressive Disorder (MDD) is marked by abnormal brain function and elevated plasma oxidative stress markers. The specific relationship between these factors in MDD remains unclear. In this study, we conducted resting-state fMRI scans on fifty-seven first-episode, drug-naive MDD patients and sixty healthy controls. Plasma levels of oxidative stress markers (superoxide dismutase (SOD) and glutathione reductase (GSR)) were assessed using ELISA. Our results revealed a positive correlation between plasma SOD and GSR levels in MDD patients and the amplitude of low-frequency fluctuation (ALFF) values in key brain regions—thalamus, anterior cingulate gyrus, and superior frontal gyrus. Further analysis indicated positive correlations between plasma SOD and GSR levels and specific ALFF values in MDD patients without suicidal ideation, with these correlations not significant in MDD patients with suicidal ideation. Additionally, seed-based whole-brain functional connectivity analysis demonstrated a negative correlation between plasma GSR levels and connectivity between the thalamus and insula, while plasma SOD levels showed a positive correlation with connectivity between the thalamus and precuneus. These findings contribute to our understanding of MDD's pathophysiology and heterogeneity, highlighting the association between plasma oxidative stress markers and functional abnormalities in diverse brain regions.