Andrew H. Smith, MD, PhD
“What drives people to keep having certain thoughts and engaging in certain behaviors, well past the point when it is adaptive?”
That is the question underlying the research of Andrew H. Smith, MD, PhD, a clinical neuroscience fellow at the Icahn School of Medicine at Mount Sinai. He is studying the brain circuitry of obsessive-compulsive disorder (OCD) at the Nash Family Center for Advanced Circuit Therapeutics (C-ACT) at Mount Sinai West.
Dr. Smith has studied compulsive behavior—a feature of several psychiatric illnesses—from multiple angles. During his doctoral work at Yale University, he studied the genetics of compulsive behaviors, with a focus on compulsion in substance use. Now he is turning his attention from genetics to brain circuitry. His current work uses implantable devices to collect data about brain activity in people with OCD, with a long-term goal of improving treatments for this challenging disorder.
“Unfortunately, many patients with OCD are not where they want to be after treatment with psychotherapy and medication. What’s unique about this study is that it builds on clinical treatment. During the course of a patient’s treatment, we offer them the opportunity to partner with us on research that allows us to uncover what is happening in their brains.” –Andrew H. Smith, MD, PhD
Dr. Smith began working at the Center during his psychiatry residency in Mount Sinai’s physician-scientist program. After graduating in 2022, he stayed to expand his research experience through the T32 postdoctoral research fellowship in psychiatry. The competitive fellowship, funded by the National Institute of Mental Health, is designed to bridge the clinician-scientist gap to translate findings in neuroscience into better treatments for patients.
In his T32 project, Dr. Smith works with participants who come to Mount Sinai for deep brain stimulation (DBS) for obsessive-compulsive disorder.
“Unfortunately, many patients with OCD are not where they want to be after treatment with psychotherapy and medication,” Dr. Smith says. “What’s unique about this study is that it builds on clinical treatment. During the course of a patient’s treatment, we offer them the opportunity to partner with us on research that allows us to uncover what is happening in their brains.”
Deep Brain Stimulation for OCD
The Center focuses on innovative research to advance the use of neuromodulation for hard-to-treat neuropsychiatric disorders. Neuromodulation includes a range of interventions, from non-invasive techniques like transcranial magnetic stimulation (TMS) to deep brain stimulation (DBS), which involves surgically implanting electrodes into brain tissue.
Under the direction of Helen Mayberg, MD, Founding Director of C-ACT and Professor, Psychiatry, Neurology, Neuroscience, and Neurosurgery, Dr. Smith is collaborating with a multidisciplinary team of experts including Martijn Figee, MD, PhD, Associate Professor, Psychiatry, Neurology, Neuroscience, and Neurosurgery; Ignacio Saez, PhD, Assistant Professor, Neurology, Neuroscience, and Neurosurgery; and Xiaosi Gu, PhD, Associate Professor, Psychiatry, and Neuroscience and Director of Mount Sinai’s Center for Computational Psychiatry.
“In my previous research in computational genetics, I learned a lot about the genetic building blocks of compulsive thoughts and behaviors. This study allows me to pursue a line of research that directly involves working with patients who really need our help,” Dr. Smith says.
The first-line therapy for OCD involves medications and psychotherapy, followed by non-invasive neuromodulation tools like TMS. When patients don’t see significant improvements from those therapies, they may be candidates for treatment with DBS.
“With DBS, we can target the deep regions of the brain that we think are holding patients back and keeping them stuck in thought and behavioral loops,” Dr. Smith says.
Researchers at the Center were already studying DBS in patients with OCD, evaluating them over the course of treatment using a battery of cognitive tests. That study is allowing the researchers to better understand which cognitive processes—such as mental flexibility or sensitivity to environmental stimuli—are changing during treatment, as a person’s symptoms improve over time. In his fellowship research, Dr. Smith is adding to that work by exploring how brain activity changes as people’s cognitive processes and behaviors change during treatment.
Such research only became possible recently, when the U.S. Food and Drug Administration cleared the use of a new generation of DBS devices that record neural activity over time, in addition to providing brain stimulation.
“Once these devices are implanted, we can study people’s brain changes directly, in a way that has never been done in patients,” Dr. Smith says. “This device allows us to ask new scientific questions in a very direct way.”
DBS for OCD and Beyond
By connecting the dots between brain activity, cognitive processes, and behaviors, Dr. Smith hopes the research will paint a more detailed picture of OCD in the brain.
“Our goal is to more fully understand how brain stimulation is leading, bit by bit, to changes in what the brain does when faced with obstacles,” he says.
The research is also an opportunity to learn more about the underlying brain circuits involved in other illnesses, including the compulsive use of substances.
“If we can learn more about the neural circuits driving compulsive thinking and behavior, we can fine-tune non-invasive interventions such as medication or TMS. Ultimately, it may help us develop better treatments for more patients, so we don’t need to rely on surgery and DBS,” he says.
The T32 fellowship is a two-year program, so Dr. Smith considers this research a pilot study to demonstrate how the new implantable devices can be used to better understand compulsive behaviors. Those data will support his application for an NIH Career Development (K) Award, which he hopes will enable him to further this line of inquiry and launch his independent research career.
“The T32 fellowship program is designed to give candidates the time and space to define their intellectual contribution to the department. It has allowed me to build on the strength of the expertise at Mount Sinai without duplicating what anyone else is already doing,” Dr. Smith says. “I am thankful to be able to work with such an incredible interdisciplinary team of mentors, doing research that can optimize techniques for helping the patient sitting in front of me.”