NEW YORK (AP) — Emily Hollenbeck lived with a deep, 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 — called deep brain stimulation, or DBS — could ultimately help many of the nearly three million Americans like them 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 body of recent research is promising, and more is being done – although two large studies that showed no benefit from using DBS for depression 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,” says Hollenbeck, who is part of ongoing research at Mount Sinai West. “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. But her first big 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 and return would sink into poverty. She ended up in the hospital.
“I ended up having a kind of on-and-off pattern,” she said. After responding to medication for a while, she relapsed.
She managed to earn a doctorate in psychology even after losing her mother in her senior year of high school. But the black hole always returned to pull her in. 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 underwent the brain surgery while sedated but awake. Dr. Brian Kopell, director of Mount Sinai’s Center for Neuromodulation, placed thin metal electrodes in a part of her brain called the 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. Hollenbeck calls it ‘continuous Prozac’.
Doctors say the stimulation helps because 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 circuitry,” he said, allowing the brain to do what it would normally do.
Hollenbeck said the effect was almost immediate.
“The first day after the operation, she started to feel a relief from her negative mood and heaviness,” says her psychiatrist, Dr. Martijn Figee. “I remember her telling me that for the first time in years she was able to enjoy Vietnamese takeaway and actually taste the food. She started decorating her house, which had been completely empty since she moved to New York.”
For Hollenbeck, the most profound change was enjoying music again.
“When I was depressed, I couldn’t listen to music. It sounded and felt like I was listening to radio static,” she said. “Then one sunny day in the summer I was walking down the street and listening to a song. I just felt this buoyancy, this, ‘Oh, I want to walk more, I want to do things!’ And I realized that I am doing better.”
She only wishes the therapy had been there for her parents.
THE HISTORY OF 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. Dr. Katherine Scangos, a psychiatrist at the University of California, San Francisco, who also researches DBS and depression, cited a number of reasons: The treatment was not personalized and researchers looked at results within a few weeks.
Some 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.
Treatments tested by different teams are now much more tailored to individuals. 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 pinpoint the exact spot where Kopell can place electrodes.
“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. “Everyone’s brain is a little different, just like people’s eyes are a little further apart or a nose is a little bigger or smaller.”
Other research teams also tailor treatment to the patient, although their methods differ slightly. Scangos and her colleagues study different targets in the brain and provide stimulation only when needed for severe symptoms. She said ultimately the best therapy may be a combination of approaches.
As teams continue to work, Abbott is launching a large clinical trial this year ahead of a possible FDA decision.
“The field is progressing quite quickly,” Scangos said. “I hope we get approval in a short time.”
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 pathways or mechanisms in the brain that cause depression, and so choosing a spot to stimulate is difficult. Selecting the right patients for DBS is also difficult, he said, and there are approved, successful treatments for depression available.
“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 gives them an objective way to observe how people get better 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 gives researchers brain recordings by logging into a tablet, placing a remote control over the pacemaker-like device in her chest and transmitting the data. She answers questions that arise about how she feels. She then records a video that is analyzed for things like facial expression and speech.
Occasionally, she enters Mount Sinai’s “Q-Lab,” an immersive environment where scientists conduct quantitative research and collect all kinds of data, including how she moves in a virtual forest or makes circles in the air with her arms. Like many other patients, she moves her arms faster now that she is doing better.
Data from admissions and visits is combined with other information, such as life events, to map out how she is doing. This helps doctors make decisions such as whether to increase her dose of electricity – which they once did.
On a recent morning, Hollenback moved her collar and brushed her hair to the side, revealing the scars on her chest and head from her DBS surgery. To her, they are signs of how far she has come.
She makes her way through the city, takes walks in the park and goes to libraries, which were a refuge in her childhood. She no longer worries that normal life problems will trigger crushing depression.
“The stress is quite extreme at times, but I can see and remember, even on a physical level, that I am doing well,” she said.
“If I hadn’t had DBS, I’m pretty sure I wouldn’t be alive today.”
___
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.