Bed nucleus of the stria terminalis-nucleus accumbens stimulation for depression: A randomized, double-blind, crossover trial
Although deep brain stimulation (DBS) shows potential in treatment-resistant depression (TRD), the efficacy remains controversial. To assess the efficacy of DBS of the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc) for TRD, we conduct a randomized, double-blind, crossover trial after an open-label optimization stage. Stimulation leads to a mean decrease in the Hamilton Depression Scale-17 (HAMD) scores of 10.1 points (p < 0.001) with a 50% response rate at the end of the open-label stage. Anxiety, quality of life, and disability are also improved. The HAMD scores are significantly lower in patients during active DBS than during sham DBS (p < 0.001). Serious adverse events include suicide (1 patient) and seizure (1 patients). With individual stimulation analysis, we identify optimal stimulation sites, fiber tracts, and functional networks (false discovery rate [FDR] p < 0.05). This study demonstrates the efficacy and safety of BNST-NAc DBS for TRD and reveals optimal brain targets for stimulation. This study was registered at ClinicalTrials.gov (NCT04530942).
Authors
- F. Wang (ORCID: https://orcid.org/0000-0002-6693-3140)
- Kejia Hu (ORCID: https://orcid.org/0000-0002-1175-3580)
- Linbin Wang (ORCID: https://orcid.org/0000-0002-4813-4337)
- Ningfei Li (ORCID: https://orcid.org/0000-0003-3315-3591)
- Xian Qiu (ORCID: https://orcid.org/0000-0002-7510-7940)
- Jinrong Zhang (ORCID: https://orcid.org/0000-0003-0774-8479)
- Yijie Zhao
- Zheng Ye (ORCID: https://orcid.org/0000-0001-5532-6428)
- Qimin Liu (ORCID: https://orcid.org/0000-0003-3840-1136)
- Xin Lv (ORCID: https://orcid.org/0000-0001-9514-3570)
- Kuanghao Ye
- Yijie Lai
- Luling Dai
- Yixin Pan
- S. Zhan
- Yingying Zhang
- Yiru Fang
- Valerie Voon
- Ti-Fei Yuan
- Wei Liu (20030)
- Chencheng Zhang
- Xiaoxiao Zhang
- Andres M. Lozano
- Yuhan Wang
- Peng Huang
- Bomin Sun
- Dianyou Li
Institutions
- Boston University (US)
- University Health Network (CA)
- Fudan University (CN)
- Toronto Rehabilitation Institute (CA)
- Ruijin Hospital (CN)
- Sir Run Run Shaw Hospital (CN)
- Shanghai Mental Health Center (CN)
- Humboldt-Universität zu Berlin (DE)
- Shanghai Institute for Science of Science (CN)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
- Krembil Research Institute
- Zhejiang University (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1016/j.xcrm.2026.102711
- Primary Topic
- Neurotransmitter Receptor Influence on Behavior
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Science and Technology Commission of Shanghai Municipality
- Shanghai Jiao Tong University
- Medical Research Council
- Fundamental Research Funds for the Central Universities
- Scientific and Innovative Action Plan of Shanghai