TXNIP and NLRP3 inflammasome markers in major depressive disorder: Associations with remission status and verbal memory.

BACKGROUND

Oxidative stress plays a role in the pathophysiology of depression and cognitive dysfunction. Oxidative stress induced NOD-like receptor 3(NLRP3) inflammasome and Thioredoxin-interacting protein (TXNIP) activation may contribute to neuroinflammation in depression. As oxidative stress contributes to insulin resistance, it may represent a shared biological pathway linking depression and diabetes. This study compared NLRP3, TXNIP, and insulin resistance in remitted and non-remitted patients with major depressive disorder (MDD) and healthy controls, and their associations with cognitive performance.

METHOD: The study included 120 non-obese participants: 40 remitted patients with MDD, 40 non-remitted patients and 40 healthy controls. Participants underwent diagnostic and neuropsychological assessments.

RESULTS

Serum NLRP3 levels were highest in the non-remitted group and lowest in healthy controls (p < 0.001). The non-remitted group also exhibited significantly higher serum TXNIP levels than both the remission and healthy control groups (p < 0.001), which did not differ from each other. Higher TXNIP levels were associated with poorer verbal memory. HOMA-IR did not differ across groups (p = 0.391).

CONCLUSION

Our findings indicate that NLRP3 and TXNIP levels differ according to remission status, with lower levels in remitted than non-remitted patients, consistent with the involvement of oxidative stress and inflammatory pathways in MDD. In contrast, HOMA-IR did not differ significantly between groups, suggesting no evidence of differences in insulin resistance by remission status in this non-obese, non-diabetic sample. In addition, TXNIP was associated with poorer verbal memory, a finding requiring cautious interpretation given its exploratory nature. Overall, NLRP3 and TXNIP may warrant further investigation as potential biomarkers associated with remission status and clinical symptoms in MDD.