Individualized Connectivity-Guided Versus Conventional Targeting of Accelerated Theta-Burst Stimulation in Depression: A Randomized, Double-Blind, Parallel-Design Trial

作者：Li M, Wu Z, Lu X, Zalesky A, Cheng X, Zhang Y, Cash RFH, Jin F, Jia S, Xiao Y, Zhong G, Zhang X, Yue W, Yang Z, Jiang T, Yan H · 发表于：The American journal of psychiatry · 年份：2026 · DOI：10.1176/appi.ajp.20251084 · 研究领域：Bipolar and Related Disorders、Depressive Disorders、Neuroimaging、Neurostimulation、TMS

OBJECTIVE: Scalp-based repetitive transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex (DLPFC) does not account for interindividual variability. This trial was designed to determine whether individualized connectivity-guided intermittent theta-burst stimulation (iTBS) improves antidepressant outcomes compared with 5-cm targeting. METHODS: In this single-center, randomized, double-blind, three-arm trial (February 2023-March 2025), adults ages 18-65 years with major depressive disorder or bipolar II depression (≥1 antidepressant failure) were randomly assigned to receive 20 sessions of iTBS over 2 weeks using robotic neuronavigation with one of three targeting strategies: 5-cm rule, functional connectivity (FC)-guided targeting showing negative resting-state connectivity with the subgenual anterior cingulate cortex (sgACC), or structural connectivity (SC)-guided sites defined by probabilistic tractography to the sgACC. The primary outcome was percentage reduction in 17-item Hamilton Depression Rating Scale (HAM-D) score at week 2. Secondary outcomes included HAM-D score reduction at weeks 6 and 12, response or remission, self-reported symptoms, performance on a cognitive battery, and adverse events. RESULTS: Of 123 randomized participants, 119 were included in the modified intention-to-treat analyses (5-cm, N=40; SC-guided, N=39; FC-guided, N=40). SC-guided iTBS produced significantly greater HAM-D score reduction than the 5-cm rule at week 2 (l...