This study investigates whether combining virtual reality mindfulness-based cognitive therapy (VR-MBCT) with transcranial direct current stimulation (tDCS) can effectively treat depression occurring after a stroke (post-stroke depression, PSD). The goal is to determine if this combined approach is more beneficial than either treatment alone or standard care in alleviating depressive symptoms.

The study will enroll adults aged 18-65 who have experienced a stroke within the past week, are medically stable, and exhibit moderate to severe depression symptoms. Participants must be right-handed and able to undergo MRI scans and study assessments. Individuals with certain neurological or psychiatric conditions, other major health issues, or specific contraindications for tDCS will not be eligible.

Procedures:

This is a randomized controlled trial lasting approximately 28 weeks, divided into two phases. In the first phase (8 weeks), participants are randomly assigned to one of four groups:

Group 1: Receives sham (placebo) versions of both VR-MBCT and tDCS plus standard medication.

Group 2: Receives active tDCS and sham VR-MBCT plus standard medication. Group 3: Receives active VR-MBCT and sham tDCS plus standard medication. Group 4: Receives both active VR-MBCT and active tDCS plus standard medication. Treatments are administered 5-6 times per week for 4 weeks, followed by a 4-week blinded follow-up.The primary outcome is the change in depression scores (HDRS-24、PHQ-9) from baseline to 8 weeks. Secondary outcomes include rates of clinical response, remission, relapse, treatment acceptability, and changes in anxiety, sleep quality, and daily functioning.

Inclusion Criteria:

1. Aged 18 to 65 years (inclusive).
2. Stroke onset ≥ 4 weeks, with stable condition and an NIHSS score ≤ 15.
3. Right-handed.
4. Patient must be in a depressive episode, defined by a PHQ-9 score ≥ 5 and confirmed by a HDRS-24 score ≥ 8.
5. Has not used any antidepressants before the enrollment.
6. No contraindications to tDCS (e.g., metal plates in the head, brain implants, aneurysm clips, cochlear implants, cardiac pacemakers, etc.).
7. Has not received systematic psychotherapy (such as MBCT, mindfulness training, or cognitive behavioral therapy) for the current or previous depressive episodes.
8. Has more than 8 years of formal education.
9. Has not received tDCS or other transcranial electrical stimulation treatment for the current or previous depressive episodes.
10. Is able to cooperate with multimodal MRI data collection and follow-up assessments, and can understand and comply with the study requirements.

Exclusion Criteria:

1. History of treatment-resistant depression, defined as failure to respond to at least two different antidepressant medications of adequate dosage and duration (at least 8 weeks at the maximum recommended therapeutic dose).
2. Other psychiatric diagnoses (e.g., intellectual disability, schizophrenia, affective psychosis, bipolar disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, eating disorders, personality disorders, substance use disorders, post-traumatic stress disorder, panic disorder, or social phobia). Co-morbid anxiety disorder is acceptable.
3. Baseline Mini-Mental State Examination (MMSE) score ≤ 24.
4. Presence of suicidal ideation or plan within 4 weeks prior to baseline.
5. Depressive symptoms are better explained by another clinical condition (e.g., hypothyroidism, anemia, congestive heart failure) or other mental disorders.
6. Presence of severe, unstable cardiovascular, hepatic, renal, hematological, endocrine diseases, or malignancies.
7. Laboratory tests indicating significant impairment: total bilirubin (TBIL) > 1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times ULN; glomerular filtration rate (GFR) ≤ 70 mL/min; or thyroid-stimulating hormone (TSH) outside the normal range.
8. Poorly controlled hypertension (sitting systolic blood pressure (SBP) ≥ 180 mmHg or sitting diastolic blood pressure (DBP) ≥ 110 mmHg at screening or baseline).
9. Epilepsy and/or other neurological diseases (e.g., dementia, traumatic brain injury, Parkinson's disease, Huntington's disease, multiple sclerosis), or any neurological condition leading to increased intracranial pressure, brain damage, or increased risk of seizures.
10. Pregnant, lactating, or planning pregnancy.
11. Significant visual or hearing impairment that prevents participation in interventions or assessments.
12. Received brain stimulation therapy (e.g., ECT, mECT, TMS, rTMS, deep brain stimulation, vagus nerve stimulation) within 3 months prior to baseline.
13. Participation in another clinical trial within 1 month prior to baseline (excluding screening failures).
14. Any other condition deemed by the investigator as unsuitable for participation in the study.