Cell Rep Med. 2026 Mar 31:102711. doi: 10.1016/j.xcrm.2026.102711. Online ahead of print.
ABSTRACT
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).
PMID:41923626 | DOI:10.1016/j.xcrm.2026.102711
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