An often arduous condition, according to the World Health Organization, 280 million people worldwide suffer from severe depression. A third of these people are unresponsive to existing treatments such as therapy, pharmaceuticals, or electrostimulation of the brain. This untreatable or intractable form of depression can be life-threatening, with many sufferers regularly hospitalized, having an exceedingly low quality of life with little hope of respite.
However, an end is now in sight, according to researchers at the University of California, San Francisco (UCSF), who successfully treated intractable depression using a highly personalized treatment. The patient, identified only as Sarah, had her unique treatment-resistant depression mapped and then counteracted with deep brain stimulation (DBS). After which, the team saw instant results: “When we turned this treatment on, our patient’s depression symptoms dissolved, and in a minimal time she went into remission,” Dr. Katherine Scangos, a psychiatrist and neuroscience specialist at UCSF who led the study team, told reporters. The UCSF researchers hailed their achievement, published in Nature Medicine, as a landmark in the effort to develop personalized treatments for depression using electroceuticals.
Using personalized medicine to treat depression
During the past two decades, a pacemaker system for the brain known as DBS has successfully treated a legion of patients with Parkinson’s disease or epilepsy. However, the majority of trials involving depression have ended in disappointment. Because the brain does not appear to have just one region for depression – several interconnected areas can be in play, the combination of which differs between people. Additionally, studies involving DBS for depression used simpler devices that delivered stimulation continuously in one place, giving inconsistent results. Still, DBS has become the gold standard treatment for epilepsy and Parkinson’s disease, with specific brain circuits identified for stimulation.
Historically, therapeutics for depression encompasses a “one-size-fits-all” approach. In comparison, the method developed by the UCSF team takes into account the fact that in different people, depression may involve distinctive areas of the brain personalized to that patient and identifies individualized biomarkers. Meaning, for the first time, neuroscientists have mapped and regulated a personalized brain circuit uniquely associated with depression.
To this end, the UCSF researchers discovered a neural biomarker, a specific pattern of brain activity indicating the onset of depression in the patient, and customized a commercial device to recognize that pattern and electrically stimulate specific brain regions. To identify the exact brain activity pattern linked to Sarah’s unique depression circuit, the lab conducted a 10-day exploration of her brain, placing fine wires known as electrodes into mood-related neural regions. She was then asked about her feelings while small pulses of electricity were delivered across the areas one by one, with her response recorded. The results guided the placement of the neuromodulation system in Sarah’s right brain hemisphere, where its electrodes extended into two neural networks. One was the amygdala, where changes could “predict when her symptoms were most severe,” and the other was the ventral striatum, involved in emotion, motivation, and reward, where stimulation “consistently eliminated her feelings of depression,” Dr. Scangos said.
A new way of life for sufferers with untreatable depression
The meticulous, personalized approach paved the way for the initial phase lasting a week, where an interim brain implant recorded a varied range of activity. At the same time, Sarah regularly logged her mood on a tablet. A machine-learning algorithm was then applied to identify a telltale pattern of activity in the amygdala region accompanying Sarah’s lowest points. Regarding this initial phase, Sarah felt that: “My daily life had become so restricted and impoverished by depression that I felt tortured by each day and forced myself to resist the suicidal impulses that overtook me several times an hour.” Adding, “When I first received stimulation, I felt the most intensely joyous sensation, and my depression was a distant nightmare for a moment. I just laughed out loud. It’s the first time I had spontaneously laughed or smiled in five years.”
The device, about the size of a matchbox, was surgically implanted following the initial phase, creating an immediate “on-demand” therapy unique to Sarah and the neural circuit that triggers her treatment-resistant depression. The individualized treatment happens about 300 times each day, equivalent to about 30 minutes of stimulation. Sarah said no sensation accompanies the electrical pulse, aside from a subtle feeling of alertness and positivity. “At first, within a few weeks, the suicidal thoughts just disappeared. Then it was just a gradual process. It was like my lens on the world changed,” Sarah said.”Everything has gotten easier and easier and easier.”
Commenting on the singular nature of this procedure, Jonathan Rosier, professor of neuroscience and mental health at University College London, asserts: “This is an exciting step forward due to the bespoke nature of the stimulation. It is likely that if trialed in other patients, different recording and stimulation sites would be required, as the precise brain circuitry underlying symptoms probably varies between individuals.”
The team hopes that their personalized electroceutical can be tested in much more extensive trials and eventually bring relief to many sufferers of long-term, treatment-resistant depression. To this end, Dr. Scangos has recruited two more patients with severe depression to take part and aims for 12 volunteers altogether. “We have a lot left to learn about variability across different patients and different types of depression,” she ends.
Image courtesy of John Lok for the University of California, San Francisco (UCSF).
Readers can find the opensource study in the journal Nature Medicine.
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