Mount Sinai Study Points Toward More Precise Treatment for Severe Depression
Mount Sinai researchers announced new findings on October 13, 2026, that could help refine an experimental treatment for severe depression. The study, published October 1 in the American Journal of Psychiatry, examines why some people experience lasting improvement after deep brain stimulation while others do not. Read Mount Sinai’s announcement.
Researchers analyzed existing data from 131 people with treatment-resistant depression across three independent patient groups. They compared clinical improvement with models showing which brain tissue and connections were reached by electrical stimulation. This was a retrospective analysis of patients who had already received treatment. Read the published study.
Deep brain stimulation, or DBS, involves surgery to implant electrodes within the brain. The electrodes connect to a device that delivers electrical pulses to selected areas. It is different from transcranial magnetic stimulation, or TMS, which stimulates the brain from outside the head without implanting electrodes. Learn how brain stimulation therapies work.
The analysis linked sustained improvement to stimulation reaching particular white matter pathways, including the left cingulum bundle and medial uncinate fasciculus. These findings support further study of targeting based on the brain’s connections, known as connectome-based targeting, to guide electrode placement more precisely.
Mount Sinai’s explanation highlights a practical challenge: an electrode can sit in the intended anatomical location without reaching all the connections associated with improvement. Mapping those connections may help researchers understand why apparently similar placements produce different outcomes.
The findings have limits. Researchers did not test whether moving electrodes to reach a missing pathway would improve symptoms. Patient-specific imaging was also unavailable for some participants, requiring the use of generalized brain maps. The study therefore identifies associations that need further testing; it does not establish that the proposed targeting approach will work for every patient.
DBS remains experimental for depression and requires careful specialist evaluation. It also carries risks associated with brain surgery, including bleeding, infection and cognitive problems. The National Institute of Mental Health distinguishes it from established options such as TMS and electroconvulsive therapy, or ECT, which have FDA-authorized uses in depression treatment.
For people whose depression has not improved with treatment, a discussion with a mental health specialist can help identify appropriate next steps, including established therapies or suitable research studies. Any changes to an existing treatment plan should be made with the treating clinician.
