NEW YORK (AP) — Emily Hollenbeck lived with recurring depression that she likened to a black hole, where gravity felt so strong and her limbs so heavy that she could barely move. She knew the disease could kill her. Both her parents had taken their own lives.
She was willing to try something extreme: having electrodes implanted in her brain as part of an experimental therapy.
Researchers say the treatment — deep brain stimulation, or DBS — could ultimately help many of the nearly three million Americans with depression that resists other treatments. It has been approved for conditions such as Parkinson’s disease and epilepsy, and many doctors and patients hope it will soon become more widely available for depression.
The treatment gives patients targeted electrical impulses, similar to a pacemaker for the brain. A growing number of studies are showing promise, and more are coming – although two large studies that showed no benefit from using DBS for depression have temporarily halted progress, and some scientists continue to raise concerns.
Meanwhile, the Food and Drug Administration has agreed to accelerate its review of Abbott Laboratories’ request to use its DBS devices for treatment-resistant depression.
“At first I was blown away because the concept of it seems so intense. For example, it is brain surgery. There are wires in your brain,” Hollenbeck said. “But I also felt like I was trying everything at that moment and was desperately looking for an answer.”
‘Nothing else worked’
Hollenbeck suffered from symptoms of depression as a child growing up in poverty and occasionally homeless. Her first major fight came in college, after her father’s suicide in 2009. Another hit during a Teach for America stint left her nearly immobilized and fearful she would lose her job in the classroom. She ended up in the hospital.
She calls it “an on-and-off pattern.” After responding to medication for a while, she relapsed.
She earned a doctorate in psychology even after losing her mother in her senior year of high school. But the black hole always returned. Sometimes, she said, she thought about taking her own life.
She said she exhausted all options, including electroconvulsive therapy, when a doctor told her about DBS three years ago.
“Nothing else worked,” she said.
She became one of only a few hundred treated with DBS for depression.
Hollenbeck was operated on while sedated but awake. Dr. Brian Kopell, director of Mount Sinai’s Center for Neuromodulation, placed thin metal electrodes in her brain’s subcallosal cingulate cortex, which regulates emotional behavior and is involved in feelings of sadness.
The electrodes are connected via an internal wire to a device placed under the skin of her chest that controls the amount of electrical stimulation and delivers constant low-voltage pulses.
Doctors say electricity speaks the language of the brain. Neurons communicate using electrical and chemical signals.
In a normal brain, Kopell said, electrical activity reverberates unhindered in all areas, in a kind of dance. In depression, dancers become stuck in the emotional circuits of the brain. DBS seems to “loosen the circuit,” he said.
Hollenbeck said the effect was almost immediate. She only wishes the therapy had been there for her parents.
THE TREATMENT
The path to this treatment goes back twenty years, when neurologist Dr. Helen Mayberg led promising early research.
But setbacks followed. Large studies started more than twelve years ago showed no significant difference in response rates for treated and untreated groups.
However, later research found that depression patients showed stable, long-lasting relief from DBS when observed for years. Overall, DBS for depression across different brain targets is associated with an average response rate of 60%, according to a 2022 study.
The Mount Sinai team is one of the most prominent studies of DBS for depression in the US. There, a neuroimaging expert uses brain images to locate the exact spot where the electrodes should be placed.
“We have a template, a blueprint of exactly where we want to go,” says Mayberg, a pioneer in DBS research and founder and director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai.
Other research teams are also adapting the treatment, although the methods differ slightly.
Abbott is launching a large clinical trial this year, ahead of a possible FDA decision.
But some doctors are skeptical and point to possible complications such as bleeding, stroke or infection after surgery.
Dr. Stanley Caroff, professor emeritus of psychiatry at the University of Pennsylvania, said scientists still don’t know the exact brain pathways or mechanisms that cause depression. And it’s also difficult to select the right patients for DBS, he said.
“I believe from a psychiatric point of view, the science is not there,” he said of DBS for depression.
MOVING FORWARD
Hollenbeck acknowledges that DBS is not a panacea; she is still on medication for depression and requires ongoing care.
She recently visited Mayberg in her office and discussed the recovery. “It’s not about being happy all the time,” the doctor told her. “It’s about making progress.”
That’s what researchers are studying now: how to track progress.
Recent research by Mayberg and others in the journal Nature has shown that it is possible to see how someone is doing at any given moment. When analyzing the brain activity of DBS patients, researchers found a unique pattern that reflects the recovery process. This provides an objective way to observe people’s improvement and distinguish between impending depression and typical mood swings.
Scientists confirm these findings using newer DBS devices in a group of patients, including Hollenbeck.
She and other participants largely contribute at home. She regularly takes brain recordings by logging into a tablet and placing a remote control above the pacemaker-like device in her chest. She answers questions about how she feels. And she records videos, analyzed for facial expression and speech, among other things.
Occasionally she goes to Mount Sinai’s “Q-Lab,” where scientists conduct quantitative research and collect all kinds of data, including how she moves in a virtual forest or makes circles with her arms. Like many other patients, she moves faster now that she is doing better.
On a recent morning, Hollenback swept her hair aside, revealing the scars on her chest and head from the DBS surgery — signs of how far she has come.
She takes walks in the park and visits libraries, which were a refuge in her childhood. She no longer worries that normal life problems will trigger crushing depression.
“If I hadn’t had DBS, I’m pretty sure I wouldn’t be alive today,” she said.
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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.