Neuroregulatory effects of combined tDCS and rTMS therapy on major depressive disorder: insights into symptom alleviation and inflammatory modulation

Major depressive disorder (MDD) is frequently characterized by elevated inflammatory markers. Transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been studied separately for the alleviation of inflammation levels in MDD. This study aims to investigate the combined neuroregulatory effects of tDCS and rTMS on neuroinflammation in patients with MDD. This 10-day, parallel-group randomized controlled trial (RCT) involved 88 patients with MDD, with 80 patients ultimately completing the study. Patients were randomly divided into four intervention groups: combination therapy (tDCS combined with rTMS, n = 20), tDCS ( n = 20), rTMS ( n = 21), and pharmacological ( n = 19) treatment, and received 10 consecutive days of treatment. The Hamilton Depression Rating Scale (HAMD-17) was used to assess changes in depressive symptoms, and cytokine levels were measured to assess inflammatory status. Compared to baseline, total HAMD-17 scores decreased post-treatment in all four groups. The response rates ( χ2 = 1.660, p = 0.646) and remission rates ( χ2 = 5.208, p = 0.157) were not significantly different between the four groups. Multivariate logistic regression analysis identified IL-2 ( p = 0.022, OR = 0.850, 95% CI: 0.740–0.977) and TNF-α ( p = 0.006, OR = 1.061, 95% CI: 1.017–1.106) levels as being independently associated with the use of combined treatment. All four treatment groups demonstrated comparable short-term efficacy in alleviating depressive symptoms. IL-2 and TNF-α represent potential prognostic biomarkers for patients with MDD.