Clustering depression subgroups based on dorsolateral prefrontal-subgenual anterior cingulate cortex peak functional connectivity reveals different symptom profiles and TMS treatment outcomes

作者：Gai Kong, Sirui Wang, Lijiang Wei, D. H. Zhang, Lei Xu, Junjie Wang, HuiRu Cui, Zhenying Qian, Hui Li, Jingjing Huang, Hongliang Zhu, Jijun Wang, Chaozhe Zhu, Yingying Tang · 发表于：BMC Medicine · 年份：2026 · DOI：10.1186/s12916-026-04806-y · 研究领域：Functional Brain Connectivity Studies、Transcranial Magnetic Stimulation Studies、Neural and Behavioral Psychology Studies

BACKGROUND: Aberrant functional connectivity (FC) between the left dorsolateral prefrontal cortex (DLPFC) and subgenual anterior cingulate cortex (sgACC) is a replicated neural correlate of major depressive disorder (MDD). Emerging evidence suggests that individualized DLPFC-sgACC peak connectivity profiles may optimize transcranial magnetic stimulation (TMS) targeting and therapeutic outcomes. We hypothesized that the heterogeneity of DLPFC-sgACC peak FC locations could serve as a neurological basis for classifying distinct MDD subgroups. METHODS: We recruited 120 patients with MDD and used resting-state functional magnetic resonance imaging (MRI) to identify the peak of DLPFC-sgACC FC. Using the personalized peaks' spatial distribution, we clustered patients with MDD into subgroups and compared between-subgroup depressive and anxiety profiles. The classification performance of different clinical profiles between the subgroups was evaluated. The TMS therapeutic outcomes were retrospectively compared between these two subgroups in a small subsample of 37 patients who completed TMS treatment. RESULTS: The personalized DLPFC-sgACC peaks of patients with MDD were spread widely within the left DLPFC, clustering into the anterior (73.3%) and posterior (26.7%) subgroups. Peaks in the anterior subgroup were closer to the group-averaged peak, whereas peaks in the posterior subgroup were localized in the posterior DLPFC. The two subgroups showed comparable depressive symptom severity;...