by NEW YORK (AP) – Emily Hollenbeck lived with a deep, recurring depression that felt like a black hole, where gravity felt so strong and her limbs so heavy she could barely move. She knew the illness could kill her. Both parents had taken their own lives.
She was willing to try something extreme: Implanting electrodes in her brain as part of an experimental therapy.
Researchers say the treatment — called deep brain stimulation, or DBS — could eventually help many of the nearly 3 million Americans like her with depression that resists other treatments. It’s approved for conditions like Parkinson’s disease and epilepsy, and many doctors and patients hope it will soon be more widely available for depression.
The treatment gives patients targeted electrical impulses, like a pacemaker for the brain. A growing body of recent research is promising, and more is underway — although two large studies showing no benefit to using DBS for depression has temporarily halted progress, and some scientists are still expressing concern.
Meanwhile, the Food and Drug Administration has agreed to speed up its review of Abbott Laboratories’ application to use its DBS devices for treatment-resistant depression.
“At first I was confused because the concept seems so difficult. Like, it’s brain surgery. You have wires embedded in your brain,” said Hollenbeck, who is part of ongoing research at Mount Sinai West. “But I also felt like I’d tried everything at that point, and I was desperate for an answer.”
“Nothing else was working”
Hollenbeck suffered from symptoms of depression as a child growing up in poverty and sometimes homelessness. But her first major bout came in college, after her father’s suicide in 2009. Another bout during Teach for America left her immobilized and anxious about losing her job in the classroom and going into poverty again. She landed in the hospital.
“I finally had some kind of pattern,” she said. After responding to medication for a while, she would relapse.
She managed to earn a doctorate in psychology, even after losing her mother in her last year of grade school. But the black hole always returned to pull her in. Sometimes, she said, she thought about ending her life.
She said she exhausted all options, including electromagnetic therapy, when a doctor told her about DBS three years ago.
“Nothing else was working,” she said.
She was one of a few hundred treated with DBS for depression.
Hollenbeck had brain surgery and was sedated but awake. Dr. Brian Kopell, who directs Mount Sinai’s Center for Neuromodulation, placed thin metal electrodes in a region of her brain called the subcallosal cingulate cortex, which controls emotional behavior and is associated with feelings of sadness.
The electrodes are connected by an internal wire to a device placed under the skin in her chest, which controls the amount of electrical stimulation and delivers continuous low-voltage pulses. Hollenbeck calls it “continuous Prozac.”
Doctors say that stimulation helps because electricity speaks the language of the brain. Neurons communicate using electrical and chemical signals.
In normal brains, Kopell said, electrical activity reverberates without inhibition in all areas, in a kind of dance. In depression, the dancers become stuck within the emotional circuitry of the brain. DBS seems to “unlock the circuit,” he said, allowing the brain to do what it would normally do.
Hollenbeck said the effect was almost immediate.
“The first day after the surgery, she started to feel an increase in that negative mood and heaviness,” said her psychiatrist, Dr. Martijn Figee. “I remember her telling me that she was able to enjoy getting out of Vietnamese for the first time in years and really taste the food. She started decorating her house, which had been completely empty since she moved to New York.”
For Hollenbeck, the biggest change was enjoying music again.
“When I was depressed, I couldn’t listen to music. It looked and felt like I was listening to radio static,” she said. “Then on a sunny summer day, I was walking down the street listening to a song. I felt this buoyancy, this, ‘Oh, I want to walk more, I want to go and do things!’ And I realized I was getting better.”
She only wishes the therapy was there for her parents.
THE HISTORY OF TREATMENT
The road to this treatment stretches back two decades, when the neurologist Dr. Helen Mayberg leads promising early research.
But difficulties arose later. Large studies conducted over a dozen 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 has also researched DBS and depression, cited a few reasons: The treatment was not personalized, and the researchers looked at results over several weeks.
Some later research showed that depressed patients experienced sustained, long-term relief from DBS when observed over years. Overall, across different brain targets, DBS for depression is associated with average response rates of 60%, said one study in 2022.
Treatments being tested by different teams are much more tailored to individuals today. The Mount Sinai team is one of the most prominent researching DBS for depression in the US Yes, a neuroimaging expert uses brain images to find the exact spot for Kopell to place electrodes.
“We have a template, a blueprint of exactly where we’re going to go,” said Mayberg, a pioneer in DBS research and founding director of The Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai. “Everybody’s brain is a little different, just like people’s eyes are a little farther apart or a nose is a little bigger or smaller.”
Other research teams also tailor treatment to patients, although their methods are slightly different. Scangos and her colleagues are studying different targets in the brain and only give stimulation when needed for severe symptoms. She said 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 pretty quickly,” Scangos said. “I expect we will have approval within a short period of time.”
But some doctors are skeptical, referring to possible complications such as bleeding, stroke or infection after surgery.
Dr. Stanley Caroff, professor emeritus of psychiatry at the University of Pennsylvania, that scientists still do not know the exact pathways or mechanisms in the brain that produce depression, which is why it is difficult to choose a location for stimulation. It is also difficult to select the right patients for DBS, he said, and he acknowledged that there are successful treatments available for depression.
“I believe from a psychiatric perspective, the science is not there,” he said of DBS for depression.
MOVING FORWARD
Hollenbeck admits that DBS is not a complete cure; she takes medication for depression and needs constant care.
She recently visited Mayberg in her office and discussed recovery. “It’s not about being happy all the time,” the doctor told her. “It’s about making progress.”
That’s what researchers are now studying – how to track progress.
Research by Mayberg and others in the journal Nature recently showed that it can provide a “read out” of how a person is doing at any given time. 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 see how people get better and distinguish between impending depression and normal mood swings.
Scientists are confirming those findings using newer DBS devices in a group of patients that includes Hollenbeck.
She and other participants mostly do their part at home. She gives researchers regular brain recordings by logging on to a tablet, placing a remote control over the pacemaker-like device in her chest and sending the data. She answers questions that come up about how she feels. She then records a video that will be analyzed for things like facial expression and speech.
From time to time, she enters Mount Sinai’s “Q-Lab,” an immersive environment where scientists conduct quantitative research to collect all kinds of data, including how she moves in a virtual forest or circles in the air with his hands. Like many other patients, she moves her arms faster now that she is feeling better.
Data from recordings and visits is combined with other information, such as life events, to track how she is doing. This helps guide doctors’ decisions, such as whether she should increase her electricity dose – which they did once.
On a recent morning, Hollenback moved her collar and brushed her hair aside to reveal scars on her chest and head from her DBS surgery. To them, they are signs of how far she has come.
She makes her way around the city, walking in the park and going to libraries, which were a haven for the youth. She no longer worries that ordinary life challenges will trigger severe depression.
“The stress is overwhelming at times, but I can see and remember, even on a physical level, that I’m going to be okay,” she said.
“If I didn’t have DBS, I’m pretty sure I wouldn’t be alive today.”
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The Associated Press Health and Science Section is supported by the Howard Hughes Medical Institute Science and Media Education Group. The AP is solely responsible for all matters.
