by NEW YORK (AP) – Emily Hollenbeck lived with 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 her parents took their lives.
She was willing to try something extreme: Implanting electrodes in her brain as part of an experimental therapy.
Researchers say the treatment — deep brain stimulation, or DBS — could eventually help many of the nearly 3 million Americans with depression who resist other treatments. It is approved for conditions including 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. There’s a growing body of research, and more is on the way — 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,” Hollenbeck said. “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. Her first major bout occurred in college, after her father’s suicide in 2009. Another bout during Teach for America left her nearly immobilized and worried she would lose her job in the classroom. She landed in the hospital.
She calls it an “on-and-off pattern”. After responding to medication for a while, she would relapse.
She earned a doctorate in psychology, even after losing her mother in her last year of grade school. But the black hole always returned. 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 underwent surgery while sedated but awake. Dr. Brian Kopell, who directs the Mount Sinai Center for Neuromodulation, placed thin metal electrodes in her brain’s 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.
Doctors say that 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.
Hollenbeck said the effect was almost immediate. She only wishes the therapy was there for her parents.
THE 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.
However, 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.
The Mount Sinai team is one of the most prominent research DBS for depression in the United States. There, a neuroimaging expert uses brain images to find the exact spot 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.
Other research teams also tailor 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, referring to possible complications such as bleeding, stroke or infection after surgery.
Dr. Stanley Caroff, professor emeritus of psychiatry of the University of Pennsylvania, that scientists still do not know the exact brain pathways or mechanisms that produce depression. And selecting the right patients for DBS is also difficult, he said.
“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 provides an objective way to see improvement in people and distinguish impending depression from 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 makes regular brain recordings by logging on to a tablet and placing a remote control over the pacemaker-like device in her chest. She answers questions about how she feels. And she records videos, which are analyzed for things like facial expression and speech.
From time to time, she enters Mount Sinai’s “Q-Lab,” where scientists conduct quantitative research to collect all kinds of data, including how she moves in a virtual forest or how she makes circles with her hands. Like many other patients, she moves faster now that she is getting better.
On a recent morning, Hollenback brushed her hair aside to reveal scars on her chest and head from DBS surgery—signs that she has arrived.
She goes for walks in the park and visits libraries, which were a refuge for the youth. She no longer worries that ordinary life challenges will trigger major 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 Section is supported by the Howard Hughes Medical Institute Science and Media Education Group. The AP is solely responsible for all matters.
