To evaluate the efficacy of tACS treatment.To determine whether tACS can accelerate symptom remission, improve clinical response rates, and facilitate the recovery of emotional and cognitive functions through standardized clinical assessments.To evaluate the safety of tACS treatment.To assess adverse events and side effects in both the intervention and control groups, ensuring the safety and tolerability of tACS in adolescent populations.

This randomized, double-blind, sham-controlled pilot trial will evaluate the efficacy and safety of transcranial alternating current stimulation (tACS) combined with sertraline in adolescents with first-episode, drug-naive major depressive disorder (MDD). Eligible participants are aged 12-18 years, meet DSM-5 criteria for a current depressive episode confirmed by K-SADS-PL, have a CDRS-R score ≥40, and have not received antidepressant treatment during the current episode.A total of 30 participants will be randomized 1:1 to receive either active tACS or sham stimulation, in addition to oral sertraline (25 mg/day in the first week, titrated to 50 mg/day thereafter). The active group will undergo 20 sessions over 4 weeks (5 sessions per week) using the NEXALIN ADI device (77.5 Hz, 15 mA, 40 minutes per session). The sham device is identical in appearance but delivers no current. Both participants and operators will remain blinded.Primary outcomes are changes in depressive symptoms, measured by the CDRS-R and BDI. Secondary outcomes include anxiety (SCARED, HAMA), global improvement (CGI-S, CGI-I), mania symptoms (YMRS), suicide risk (C-SSRS), quality of life (PedsQL4.0), sleep (PSQI), rumination (RSS), and cognition (THINC-it). Safety will be monitored through adverse events, vital signs, laboratory tests, and tolerability assessments.This pilot study will provide preliminary evidence on the potential of tACS as an adjunctive treatment for adolescent depression and inform future large-scale trials.

Inclusion Criteria:

1.Age 12-18 years; 2.Subjects met the diagnostic criteria for depression in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as determined by the Childhood Affective Disorders and Schizophrenia Questionnaire (K-SADS-PL) and were currently in a depressive episode; 3.Children's Depression Rating Scale-Revised (CDRS-R) score ≥ 40 points; 4.Not receiving any antidepressant medication during the current depressive episode.

Exclusion Criteria:

1.Other comorbid mental disorders in accordance with DSM-5 except anxiety disorders; 2.Depression with psychotic symptoms; 3.Young Mania Rating Scale (YMRS) > 13; 4.History of neurological disease (such as epilepsy, brain trauma, etc.) or serious physical disease (such as thyroid disease, lupus erythematosus, diabetes, lung, liver and kidney damage, major trauma, etc.); 5.Previous treatment with electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), tACS or other neurostimulation treatments; 6.Patients currently receiving anti-epileptic drugs or high-dose benzodiazepines; 7.History of alcohol or drug abuse or dependence; 8.Breastfeeding women or pregnant women; 9.Contraindications to MRI; 10.Currently at high risk of suicide.