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.

High-definition transcranial direct current stimulation (HD-tDCS) and repetitive transcranial magnetic stimulation (rTMS) demonstrate significant potential for improving depressive symptoms and cognitive function; however, their effectiveness varies greatly among individuals. Functional near-infrared spectroscopy enables real-time monitoring of brain function during cognitive tasks in patients with psychiatric disorders.

A 4-week longitudinal study was conducted involving 61 patients with depression and 26 healthy controls. Patients were randomly assigned to HD-tDCS, rTMS, and antidepressant (AD) groups. Changes in depressive symptoms, adverse event rates, and prefrontal cortical oxyhemoglobin concentrations were assessed.

At week 4, remission rates were 62.5% (15), 61.9% (13), and 62.5% (10) in the HD-tDCS, rTMS, and AD groups, respectively (x² = 0.002, p = 1.000). Response rates were 66.7% (16), 71.4% (15), and 68.8% (11), respectively, with no significant difference between groups (x² = 0.12, p = 0.941). All groups demonstrated significant improvement in depressive symptoms and cognitive function. The rTMS group exhibited a significantly greater decrease in Hamilton Depression Scale score compared with the HD-tDCS and AD groups. After 2 weeks of treatment, patients exhibited improved depressive symptoms and reduced activation during the verbal fluency task. However, these changes were not significantly correlated (r = −0.159 to 0.240, p = 0.121–0.988).

All patients had concomitant use of ADs, which may impact near-infrared spectroscopy signaling and have an indeterminate effect on cognition.

HD-tDCS, rTMS, and ADs were equally effective, safe, and well-tolerated. HD-tDCS and rTMS were more effective for working memory, attention, executive functioning, and mood regulation.

Post-stroke depression (PSD) is a frequent neuropsychiatric disorder following stroke which is associated with poor outcome. Neuronal Per-Arnt-Sim (PAS) domain protein 4 (Npas4) is associated with cognitive function. Npas4 expression in peripheral blood mononuclear cells (PBMCs) from patients with PSD was measured to find new therapeutic strategy.

Ischemic stroke patients (n = 152) within 1 week of stroke onset were recruited. At 3 months follow-up, the patients were divided into a PSD group (n = 77) and a stroke group (n = 75) using the Hamilton Rating Scale. Healthy subjects (n = 75) were also recruited in the study. The PSD group received 12 weeks of duloxetine treatment. Cognitive function was evaluated using the P300 test. Npas4 expression in PBMCs was measured by quantitative RT-PCR (qPCR).

Before treatment, P300 latencies in the PSD group were prolonged and the P300 amplitudes were lower than the control group (P < 0.01). Npas4 expression in the PSD group was also lower than the control group (P < 0.01). After treatment, the P300 latencies were reduced and the amplitudes were significantly elevated in the PSD group compared to that before treatment (P < 0.01). Meanwhile, Npas4 levels were significantly higher than that before treatment (P < 0.01). Npas4 expression was positively correlated to the P300 amplitudes (P < 0.05).

Changes of Npas4 expression in PBMCs are associated with cognitive impairment in PSD patients and new therapeutic options applying Npas4-related transcript mechanism could be considered in the future.