Helen Mayberg, MD: Seizing Unexpected Opportunities at Every Turn
Depression has long been considered a serious mental disorder caused by extreme stress or a chemical imbalance that is treated by psychotherapy or medication. That is, until Helen Mayberg, MD, Professor of Neurology, Neurosurgery, Psychiatry, and Neuroscience, and founding Director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai, took a different approach.
“I am a neurologist, and neurologists map signs and symptoms to specific locations in the brain,” she said. She had always seen depression as a circuit disorder and the availability of brain imaging early in her training provided a method and strategy to study a psychiatric disorder as a neurological one. “That was a novel, if not heretical, idea at the time,” Dr. Mayberg said. “Now, it’s commonplace.”
For her body of work integrating imaging techniques to reveal mechanisms of depression, Dr. Mayberg was elected to the National Academy of Sciences (NAS) in May.
Dr. Mayberg considers her career to have taken an unconventional arc. She first trained clinically in neurology at Columbia University, then did a research fellowship in nuclear medicine and functional imaging at Johns Hopkins University. Prior to joining Icahn School of Medicine at Mount Sinai, Dr. Mayberg held a series of cross-disciplinary appointments in neurology, psychiatry, radiology, neurosurgery, and neuroscience at various institutions, including Johns Hopkins, University of Texas, University of Toronto, and Emory University.
Dr. Mayberg was elected to the National Academy of Sciences along with Yasmin Hurd, PhD, Ward-Coleman Chair of Translational Neuroscience and Director of the Addiction Institute of Mount Sinai. Read more about Dr. Hurd’s achievements here.
Over the last 35 years, she had used neuroimaging techniques to study abnormal brain circuits in depressed patients, explaining not just mood, motivation, cognitive, and motor feature characteristics of depression, but also providing a systematic strategy to understand how different treatments work and how to match a patient with an optimal treatment.
Forging partnerships, breaking frontiers
A milestone in her collaborative work came about when Dr. Mayberg discovered the critical role of Brodmann area 25 of the brain, a region of the prefrontal cortex, in negative mood in healthy individuals as well as how it was targeted when antidepressant treatments were successful for depression. The area is known to play a role in mood, appetite, and sleep, but its role in depression was unknown.
Following work on Brodmann area 25, Dr. Mayberg found that deep-brain stimulation—implanted electrodes that deliver electrical stimulation to precise brain locations to treat Parkinson’s disease and epilepsy—was a potential treatment for patients with treatment-resistant depression. Mapping studies she did in the 1990s led to her testing the new treatment in 2003, in which a majority of treated patients showed long-term recovery.
Every move to a new institution has been a scientific adventure with opportunity to work in a new environment with new colleagues, Dr. Mayberg said, but a constant has always been unexpected, exciting, and important new insights. “Creative disruption seems to best describe my trajectory,” she said.
Dr. Mayberg considers transdisciplinary collaboration as the philosophical anchor of her work, one that forms the overarching mission of the Nash Family Center for Advanced Circuit Therapeutics, which she founded in 2018. “The opportunity to fully realize this vision was the condition of my move to New York,” she said.
The Center brings neurology, psychiatry, neurosurgery, imaging, physiology, engineering, and behavioral health under the same roof. Researchers are working on circuit disorders, including Parkinson’s disease, depression, and obsessive-compulsive disorder, which can be treated with deep-brain stimulation, albeit in different brain targets.
“We all knew we needed to work together so that a discovery or new method developed for one disease could inform the others,” Dr. Mayberg said, “so we’re not reinventing the wheel each time.”
Continuing progress through collaborations
Technology innovations in the last several years have further advanced the deep-brain stimulation field, providing new opportunities for Dr. Mayberg and the investigators at the Center. With the capability to read electrophysiological signals in real-time via the stimulating electrodes, researchers at the Center are working on improving delivery of deep-brain stimulation, understanding what kind of patients are most appropriate and why the treatment works.
The Center is also interested in answering more basic questions, such as whether deep-brain stimulation repairs brain circuits or promotes brain plasticity. These studies are complemented by parallel work in animal models at The Friedman Brain Institute. “I consider my research ‘bedside to bench.’ I have always taken advantage of the work of basic neuroscientists, even if their methods cannot be fully applied to human patients,” Dr. Mayberg said.
“My work has had the same basic thread over the course of 35 years: what is the neurology of depression and how do we optimally treat it; not just generally, but in individual patients,” Dr. Mayberg said. “Mount Sinai is the ultimate place for this work, with a committed set of clinicians, scientists, and engineers who share this transdisciplinary vision.”
A closer look at Dr. Mayberg’s work
Dr. Eric Nestler
Eric Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director of The Friedman Brain Institute, Dean for Academic Affairs of the Icahn School of Medicine at Mount Sinai, and Chief Scientific Officer for the Mount Sinai Health System, weighs in on what he found impressive about Dr. Mayberg’s research.
“Dr. Mayberg’s work is all translation since it’s all performed in humans,” said Dr. Nestler, “Even though her research has been tethered in basic neurobiology, thinking about how it intersects with patients is evident.”
Membership of the National Academy of Sciences—considered one of the highest honors for a scientist—comes through election by existing members only. Candidates’ entire bodies of work and contributions to the field are considered as part of the nomination process and their entries are voted on in April each year, with a maximum of 120 U.S. citizens and 30 non-citizens elected annually, according to NAS. There are currently approximately 2,400 U.S. members and 500 international members, of whom 190 have received Nobel prizes. Mount Sinai has six current faculty in the prestigious organization.
Dr. Mayberg had a longstanding track record in using brain imaging to study people with psychiatric disorders, but her breakthrough was using deep-brain stimulation to treat depression.
“What Helen did was extremely novel, especially because this was for a group of patients who had especially severe depression who did not respond to a wide range of existing treatments including electroconvulsive therapy, also known as ’shock’ therapy,” Dr. Nestler said.
The paper on using deep-brain stimulation for depression, published in Neuron in 2005, remains Dr. Mayberg’s most cited work. In her study, six patients with severe depression who had failed at least four different forms of treatment underwent the experimental stimulation procedure. All six saw improvement in clinical scores, with three achieving remission or near-remission that was sustained long term.
“It was a remarkable and brave study and she has since further developed its key findings and implications,” Dr. Nestler said.
Other notable publications from Dr. Mayberg included discovering areas of the brain that were involved in feelings of sadness, and how they exhibited dysfunction in returning to baseline state in people with depression. Dr. Mayberg considered that paper, published May 1999 in The American Journal of Psychiatry, one of her hardest to get published, but it ultimately led to her work with deep-brain stimulation.
“We recruited Dr. Mayberg because we had a great deal of confidence in her multidisciplinary approach,” Dr. Nestler said. “With the additional resources possible at Mount Sinai, she can take the program to the next level.”