Abstract
BACKGROUND: In worldwide, the prevalence of depression among university students raises year by year. Although current interventions for depression may be effective, only about one-third experiencing complete response. There is a critical need for more effective, precision, and personalized approaches for depression. High-definition transcranial direct current stimulation (HD-tDCS) shows promise as a potential intervention in depression, yet its optimal stimulation parameters and neural mechanisms remain unclear. In this study, we aim to evaluate the effectiveness of magnetic resonance imaging (MRI)-guided HD-tDCS in depression among university students and explore its neural mechanisms. METHOD: In this stepped-wedge cluster randomized controlled trial, all participants will be randomly assigned to four groups. During the intervention, all groups will receive sham stimulation at week 1. With each subsequent week, one group will transition to active intervention. All groups will be receiving active intervention in week 5. Structural MRI data for each participant will be acquired to select the optimal electrode placement and correct for individual anatomical differences. The central anodal electrode will be positioned over the left dorsolateral prefrontal cortex (DLPFC), and four return electrodes will be placed 3.5 cm from the central electrode to form a circular current loop. The HD-tDCS will be delivered at a current intensity of 2 mA for 30 min per day, 5 days per week. Psychological assessment will conduct at week 0 (baseline), 1-5, and 9. MRI measurements will be performed before and after HD-tDCS. The primary outcome measures are changes in the Hamilton Rating Scale for Depression (HAMD) and Patient Health Questionnaire-9 (PHQ-9). Secondary outcomes are severity of anxiety, insomnia, and stress. Furthermore, we will employ functional near-infrared spectroscopy (fNIRS) and MRI to explore the neural mechanisms underlying the effects of HD-tDCS on depression. DISCUSSION: This study will facilitate the development of precision interventions for depression at an individual level. Multi-modal imaging approaches will provide a deepened insight into the role of MRI-guided HD-tDCS in depression and may ultimately improve intervention strategies among university students. TRIAL REGISTRATION: This study is registered in https://www.chictr.org.cn/ under protocol registration number ChiCTR2400094235 (date of registration: 19. December. 2024). Recruitment will start in March 2025.