High-Intensity Transcranial Alternating Current Stimulation for Emotion Regulation and Attentional Bias in Adolescents With Nonsuicidal Self-Injury: A Randomized Clinical Trial.

Importance: Nonsuicidal self-injury (NSSI)-a major threat to adolescents with major depressive disorder (MDD), substantially raising hospitalization and suicidality risk-stems from core deficits in emotion regulation and attentional bias toward self-injurious cues, yet current interventions are limited by slow onset and poor accessibility. Objective: To evaluate the efficacy and safety of high-intensity transcranial alternating current stimulation (HI-tACS), delivered at 77.5 Hz and 15 milliamperes, in targeting core deficits of emotion dysregulation and attentional bias in adolescents with MDD and NSSI. Design, Setting, and Participants: This double-blind, sham-controlled randomized clinical trial was conducted at a psychiatric hospital in Western China. Eligible adolescents aged 12 to 18 years diagnosed with comorbid MDD and NSSI were enrolled between October 2025 and January 2026. Data were analyzed in February 2026. Interventions: Participants were randomly assigned (1:1) to active or sham treatment groups. Each participant received treatment twice daily for 3 weeks, totaling 30 sessions. Main Outcomes and Measures: The primary outcome was the change in total score on the Difficulties in Emotion Regulation Scale after the intervention. Secondary outcomes included changes in the attentional bias index (via a dot-probe task), scores on the Emotion Regulation Questionnaire, and the Hamilton Depression Rating Scale. Results: Of 60 enrolled adolescents (mean [SD] age, 14.22 [1.11] years; 48 [80%] female), baseline characteristics were well balanced between the active (30 participants) and sham (30 participants) groups. In the intention-to-treat analysis, emotion regulation scores declined significantly from baseline to posttreatment in the active HI-tACS group (121.38 [95% CI, 119.62 to 123.14] vs 108.15 [95% CI, 106.30 to 109.99]; P < .001) but not in the sham group (119.74 [95% CI, 118.09 to 121.39] vs 117.99 [95% CI, 116.27 to 119.72]). Attentional bias toward NSSI cues also decreased more with active treatment (F = 10.34; P = .002; ηp2 = 0.169). Depression scores also decreased significantly more in the active treatment group than the sham group (estimated mean difference, -2.78 [95% CI, -4.12 to -1.44]; P < .001). Adverse event rates were comparable between active and sham groups (8 participants [29.6%] vs 3 participants [10.7%] reporting ≥1 adverse event). Conclusions and Relevance: In this randomized clinical trial of 60 adolescents with MDD and comorbid NSSI, HI-tACS was an effective and well-tolerated intervention that simultaneously improved core emotional and cognitive deficits in this population. Trial Registration: chictr.org.cn Identifier: ChiCTR2500110319.