From the Journals

Customized brain stimulation: New hope for severe depression


Personalized deep brain stimulation (DBS) appears to rapidly and effectively improve symptoms of treatment-resistant depression, new research suggests.

A doctor talks to a patient who is depressed KatarzynaBialasiewicz/Getty Images

In a proof-of-concept study, investigators identified specific brain activity patterns responsible for a single patient’s severe depression and customized a DBS protocol to modulate the patterns. Results showed rapid and sustained improvement in depression scores.

“This study points the way to a new paradigm that is desperately needed in psychiatry,” Andrew Krystal, PhD, Weill Institute for Neurosciences, University of California, San Francisco, said in a news release.

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,” Dr. Krystal added.

The findings were published online Oct. 4 in Nature Medicine.

Closed-loop, on-demand stimulation

The patient was a 36-year-old woman with longstanding, severe, and treatment-resistant major depressive disorder. She was unresponsive to multiple antidepressant combinations and electroconvulsive therapy.

The researchers used intracranial electrophysiology and focal electrical stimulation to identify the specific pattern of electrical brain activity that correlated with her depressed mood.

They identified the right ventral striatum – which is involved in emotion, motivation, and reward – as the stimulation site that led to consistent, sustained, and dose-dependent improvement of symptoms and served as the neural biomarker.

In addition, the investigators identified a neural activity pattern in the amygdala that predicted both the mood symptoms, symptom severity, and stimulation efficacy.

The patient was implanted with the Food and Drug Administration–approved NeuroPace RNS System. The device was placed in the right hemisphere. A single sensing lead was positioned in the amygdala and the second stimulation lead was placed in the ventral striatum.

When the sensing lead detected the activity pattern associated with depression, the other lead delivered a tiny dose (1 milliampere/1 mA) of electricity for 6 seconds, which altered the neural activity and relieved mood symptoms.

Remission achieved

Once this personalized, closed-loop therapy was fully operational, the patient’s depression score on the Montgomery-Åsberg Depression Rating Scale (MADRS) dropped from 33 before turning treatment ON to 14 at the first ON-treatment assessment carried out after 12 days of stimulation. The score dropped below 10, representing remission, several months later.

The treatment also rapidly improved symptom severity, as measured daily with Hamilton Depression Rating Scale (HAMD-6) and visual analog scales.

“Success was predicated on a clinical mapping stage before chronic device placement, a strategy that has been utilized in epilepsy to map seizure foci in a personalized manner but has not previously been performed in other neuropsychiatric conditions,” the investigators wrote.

This patient represents “one of the first examples of precision psychiatry – a treatment tailored to an individual,” the study’s lead author, Katherine Scangos, MD, also with UCSF Weill Institute, said in an interview.

She added that the treatment “was personally tailored both spatially,” meaning at the brain location, and temporally – the time it was delivered.

“This is the first time a neural biomarker has been used to automatically trigger therapeutic stimulation in depression as a successful long-term treatment,” said Dr. Scangos. However, “we have a lot of work left to do,” she added.

“This study provides proof-of-principle that we can utilize a multimodal brain mapping approach to identify a personalized depression circuit and target that circuit with successful treatment. We will need to test the approach in more patients before we can determine its efficacy,” Dr. Scangos said.


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