Personalized Brain Stimulation Can 'Mute' Severe Depression, Says Study

Scientists have made a landmark achievement — demonstrating personalized neuromodulation and providing relief to at least one patient suffering from treatment-resistant depression in minutes, according to a new study published in the journal Nature Medicine.

While still in a five-year clinical trial, this could revolutionize treatment for the roughly 30% of people with severe depression who may have exhausted all conventional means of treatment.

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Personalized brain stimulation reduced severe depression symptoms

The new approach is under development to sharpen its potential for treating a substantial population of people suffering from severe depression — who don't respond to existing therapies and demonstrate a high suicide risk, according to a blog post shared on the University of California San Francisco's (UCSF's) official website.

"The brain, like the heart, is an electrical organ, and there is a growing acceptance in the field that the faulty brain networks that cause depression — just like epilepsy or Parkinson's disease — could be shifted into a healthier state by targeted stimulation," said Assistant Professor Katherine Scangos in UCSF's department of psychiatry and behavioral sciences, who is also the corresponding author of the new study, in the blog post.

Mapping mild stimulation of mood-related brain sites

"Prior attempts to develop neuromodulation for depression have always applied stimulation in the same site in all patients, and on a regular schedule that fails to specifically target the pathological brain state," added Scangos. "We know depression affects different people in very different ways, but the idea of mapping out individualized sites for neuromodulation that match a patient's particular symptoms had not been well explored."

In the new case study, Scangos and colleagues successfully mapped the effects of applying a mild stimulation to multiple mood-related brain sites inside a patient who is experiencing severe treatment-resistant depression.

Proof-of-concept could serve as new foundation

The scientific team discovered how stimulation at varying sites may relieve distinct symptoms of the brain-centered disease — successfully reducing anxiety, restoring pleasure in daily activities, boosting energy levels — and, crucially, the neurological sites of stimulation depended on the real-time mental state of the patient.

This proof-of-concept study sets a much-needed foundation for a significant five-year clinical trial of Scangos' — called the PRESIDIO trial, which aims to evaluate the effectiveness of personalized neuromodulation in 12 patients suffering from severe treatment-resistant depression.

New framework for personalizing depression treatment

This trial will add to the in-progress study via the identification of brain signatures capable of reflecting participants' real-time symptoms. Using this information, scientists can program neuromodulation equipment for real-time responses to faulty network states — applying targeted stimulation capable of bringing patients' brain circuitry back into balance.

"We've developed a framework for how to go about personalizing treatment in a single individual, showing that the distinctive effects of stimulating different brain areas are reproducible, long-lasting and state-dependent," said Andrew Krystal, co-senior author of the study and director of UCSF's Dolby center, who is also the Ray and Dagmar Dolby distinguished professor of psychiatry and behavioral sciences.

Personalized brain stimulation could help 30 percent of severe depression patients

"Our trial is going to be groundbreaking in that every person in the study is potentially going to get a different, personalized treatment, and we will be delivering treatment only when personalized brain signatures of a depressed brain state indicate treatment is needed," added Krystal in the blog post.

This breakthrough study involving a five-year depression trial came on the heels of epilepsy studies. And as one of the most common psychiatric disorders — afflicting up to 264 million people globally and linked to hundreds of thousands of deaths annually — up to 30% of patients simply show no response to conventional treatments, like medication and psychotherapy. While some of this subset respond to more drastic interventions like electroconvulsive therapy (ECT), it appears we may soon see the dawn of a new alternative — in the form of personalized brain stimulation.