Predictive roles of serum IL-33/ST2 and BDNF in depressed patients with repetitive transcranial magnetic stimulation: a pilot study

Background Major depressive disorder (MDD) is considered a serious public health issue and adversely affects individuals’ quality of life. Repetitive transcranial magnetic stimulation (rTMS) is a crucial strategy for treating MDD. This pilot study aims to investigate the relationship between serum IL-33/ST2 and BDNF levels and treatment improvement in MDD patients receiving rTMS therapy. Methods This prospective study enrolled 36 patients diagnosed with MDD (under the DSM-5 diagnostic criteria) between July 2023 and July 2024. All patients underwent standard 10 Hz high-frequency rTMS for the left dorsolateral prefrontal cortex (DLPFC) for 4 weeks (totaling 20 sessions). Fasting venous blood was collected before treatment and at the end of treatment. Serum levels of IL-33, sST2, 5-HT, IL-6, and BDNF were measured using ELISA. Clinical efficacy was assessed using the Hamilton Depression Rating Scale-17 items (HAMD-17), with a reduction rate ≥50% defined as treatment response. Statistical analyses included correlation analysis, intergroup comparisons, and ROC curves, and analyses of pre-to-post-biomarker changes ( Δ ) in relation to both response status and symptom reduction. Results A total of 36 MDD patients received rTMS treatment for 4 weeks. Among them, 20 patients (55.6%) responded significantly. At baseline, serum IL-33 levels were positively correlated with HAMD-17 scores (r = 0.41, FDR-adjusted q = 0.02), whereas sST2 levels were negatively correlated (r = −0.68, FDR-adjusted q < 0.001). After rTMS treatment, those responders exhibited significantly lower serum IL-33 levels (FDR-adjusted q = 0.007) but higher BDNF levels (FDR-adjusted q = 0.005) compared to those non-responders. Those responders also had significantly greater increases in BDNF (ΔBDNF, FDR-adjusted q = 0.0004) and sST2 (ΔsST2, FDR-adjusted q = 0.021) compared to non-responders. ΔBDNF levels ( ρ = 0.499, FDR-adjusted q = 0.0049) were positively while ΔIL-33 levels (r = −0.477, FDR-adjusted q = 0.0054) were negatively correlated with symptom improvement. ROC analysis revealed that baseline 5-HT levels could predict treatment response (AUC = 0.834, p < 0.001), and post-treatment IL-33 (AUC = 0.916, p < 0.001) and BDNF (AUC = 0.916, p < 0.001) levels were significantly associated with rTMS treatment response. Conclusion Effective rTMS treatment in MDD patients is associated with decreased serum IL-33 levels and increased BDNF levels. The IL-33/ST2 and BDNF pathways may be involved in the antidepressant mechanism of rTMS.