Integrated biomarkers of oxidative stress NLRP3 inflammasome and kynurenine pathway reflect disease severity and diagnostic discrimination in depression
TL;DR
Serum levels of kynurenine, NLRP3, and 8-OHdG are all markedly increased in depression and together offer helpful diagnostic data, implying potential utility as complementary biological markers for diagnosing depression and describing its underlying pathophysiology, notwithstanding their modest relationships with symptom severity.
Abstract
Depression is associated with dysregulation of oxidative stress and inflammatory pathways. Serum biomarkers such as 8-hydroxy-2′-deoxyguanosine (8-OHdG), NLRP3, and kynurenine may reflect these pathological processes and relate to disease severity. This study evaluated the clinical relevance of these biomarkers in patients with depression and their association with symptom severity. A total of 50 patients with depression and 50 healthy controls were assessed. Serum levels of 8-OHdG, NLRP3, and kynurenine were measured. Depression severity was evaluated using the Hamilton Depression Rating Scale (HAM-D) and Patient Health Questionnaire-9 (PHQ-9). Correlations, multiple linear regression, and multivariate logistic regression. Bonferroni and Benjamini–Hochberg corrections were applied. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Patients with depression exhibited significantly higher levels of 8-OHdG, NLRP3, and kynurenine (all p < 0.05). Among the evaluated biomarkers, only 8-OHdG demonstrated a weak inverse correlation with PHQ-9 scores and a positive correlation with disease duration, whereas no significant associations were observed for other markers. In multivariable regression analyses, 8-OHdG showed nominal association with PHQ-9 scores; however, this relationship did not remain significant after correction for multiple comparisons. Multivariate logistic regression demonstrated independent associations of all three biomarkers with depression status without evidence of significant multicollinearity. ROC analysis showed moderate diagnostic performance for individual biomarkers, while the combined biomarker model achieved superior discrimination between patients and controls (AUC = 0.857). Serum levels of kynurenine, NLRP3, and 8-OHdG are all markedly increased in depression and together offer helpful diagnostic data. These indicators’ combined performance implies potential utility as complementary biological markers for diagnosing depression and describing its underlying pathophysiology, notwithstanding their modest relationships with symptom severity. Larger prospective trials are necessary for additional validation.