UCSF Health physicians have successfully treated a patient with severe depression by tapping into the specific brain circuit involved in depressive brain patterns and resetting them using the equivalent of a pacemaker for the brain.

The study, which appears in the Oct. 4, 2021, issue of Nature Medicine, represents a landmark success in the years-long effort to apply advances in neuroscience to the treatment of psychiatric disorders.

This study points the way to a new paradigm that is desperately needed in psychiatry,. We’ve developed a precision-medicine approach that has successfully managed our patient’s treatment-resistant depression by identifying and modulating the circuit in her brain that’s uniquely associated with her symptoms.
Andrew Krystal, PhD, professor of psychiatry and member of the UCSF Weill Institute for Neurosciences.

The path to this project at UC San Francisco began with a large, multicenter effort sponsored under President Obama’s BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative in 2014.

Through that initiative, UCSF neurosurgeon Edward Chang, MD, and colleagues conducted studies to understand depression and anxiety in patients undergoing surgical treatment for epilepsy, for whom mood disorders are also common. The research team discovered patterns of electrical brain activity that correlated with mood states and identified new brain regions that could be stimulated to relieve depressed mood. 

With results from the previous research as a guide, Chang, Krystal, and first author Katherine Scangos, MD, PhD, all members of the Weill Institute, developed a strategy relying on two steps that had never been used in psychiatric research: mapping a patient’s depression circuit and characterizing her neural biomarker.

This new study puts nearly all the critical findings of our previous research together into one complete treatment aimed at alleviating depressio.
,Edward Chang, who is co-senior author with Krystal on the paper and the Joan and Sanford Weill Chair of Neurological Surgery.

The team evaluated the new approach in June 2020 under an FDA investigational device exemption, when Chang implanted a responsive neurostimulation device that he has successfully used in treating epilepsy.

We were able to deliver this customized treatment to a patient with depression, and it alleviated her symptoms. We haven’t been able to do this the kind of personalized therapy previously in psychiatry.
Katherine Scangos

While the approach appears promising, the team cautions that this is just the first patient in the first trial.

There’s still a lot of work to do. We need to look at how these circuits vary across patients and repeat this work multiple times. And we need to see whether an individual’s biomarker or brain circuit changes over time as the treatment continues.
Katherine Scangos, who has enrolled two other patients in the trial and hopes to add nine more. “

FDA approval for this treatment is still far down the road, but the study points toward new paths for treating severe depression. Krystal said that understanding the brain circuits underlying depression is likely to guide future non-invasive treatments that can modulate those circuits.

 

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