This randomized, double-blind, sham-controlled clinical trial aims to evaluate the efficacy and underlying biological mechanisms of HD-tDCS targeting the primary somatosensory cortex in adolescents with bipolar depression. Participants will be randomly assigned to receive either active HD-tDCS or sham stimulation, in addition to routine clinical care. Biological data, including neuroimaging, blood biomarkers, voice and facial features, Photoplethysmography (PPG), Electroencephalography (EEG), and behavioral data, will be collected to explore potential predictors of treatment response.

This study aims to evaluate the efficacy and underlying biological mechanisms of HD-tDCS targeting the primary somatosensory cortex (S1) in adolescents with bipolar depression. Participants will be randomly assigned (1:1) to receive either active HD-tDCS or sham stimulation for 10 consecutive days (twice daily, 20 minutes each session), in addition to standard clinical care.

Multimodal assessments will be conducted at baseline, mid-treatment (after 10 sessions), and post-treatment, including clinical symptom scales, neurocognitive evaluations, structural and functional MRI, blood biomarkers (15ml of peripheral blood), as well as digital phenotyping data such as voice, EEG, PPG, sleep, and behavioral metrics.

The study also aims to identify objective biomarkers predictive of treatment response and to elucidate the neurobiological mechanisms associated with HD-tDCS applied to the S1 region. All procedures including MRI, tDCS, and assessments are non-invasive and free of charge for participants. The total duration of data collection and follow-up is expected to span approximately two years.

Inclusion Criteria:

• Between 12 and 18 years of age;
• Participants fulfill the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria for bipolar disorder (BD). Participants are assessed by the Structured Clinical Interview for DSM-IV for Axis I Disorders (SCID-I, patients' age ≥18 years old), or the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K- SADS-PL, patients' age< 18 years old);
• A current moderate or severe depressive episode defined by HAMD≥17 and Young Mania Rating Scale (YMRS) <12;
• Participants receive a stable psychotropic medication regimen prior to randomization to the trial and are willing to remain on the stable regimen during the HD-tDCS treatment phase;
• Participants and 1 or 2 parents (patients' age< 18 years old) provide informed consent after the detailed description of the study.

Exclusion Criteria:

• Prior rTMS or tDCS or electroconvulsive therapy (ECT) treatment or standard psychological therapy within 6 months prior to screening;
• Comorbidity of other DSM-IV axis I disorders or personality disorders;
• Judged clinically to be at serious suicidal risk;
• Diabetes mellitus, hypertension, vascular and infectious diseases and other major medical comorbidities;
• Unstable medical conditions, e.g., severe asthma;
• Neurological disorders, e.g., history of head injury with loss of consciousness for ≥ five minutes, cerebrovascular diseases, brain tumors and neurodegenerative diseases;
• Mental retardation or autism spectrum disorder;
• Contraindications to MRI (e.g., severe claustrophobia, pacemakers, metal implants);
• Contraindications to tDCS (e.g., metal in head, history of seizure, EEG test suggesting high risk of seizure, known brain lesion);
• Current drug/alcohol abuse or dependence;
• Pregnant or lactating female.