Efficacy and Safety of Task-specific, Biomarker-driven, HD-ctACS inTRD.

This is a single-center, randomized, double-blind, sham-controlled, crossover exploratory clinical trial designed to evaluate the therapeutic effects of task-specific, biomarker-driven HD-ctACS on treatment-resistant depression (TRD). The study will enroll 10 patients diagnosed with TRD. Each participant will, in a randomized order, undergo a 4-week active HD-ctACS treatment period and a 4-week sham stimulation (delayed HD-ctACS) period, separated by an 8-week washout period. The primary objective is to assess the efficacy of HD-ctACS in improving core depressive symptoms, with the primary outcome being the difference in the Hamilton Depression Rating Scale (HAMD) total score between the end of the two intervention periods. Secondary objectives include evaluating the safety of the therapy, its effects on other symptom dimensions, and exploring its modulatory effects on neurobiological markers of emotional processing (e.g., NAc gamma power). The total participation time for each subject is approximately 16 weeks.