A three-year, $4.5 million grant from BD2: Breakthrough Discoveries for thriving with Bipolar Disorder to Weill Cornell Medicine investigators, in collaboration with Stanford Medicine, will support a three-pronged research project to map the brain circuits that contribute to mood shifts in bipolar disorder and help develop personalized therapies for the condition.
BD2 is a $100+ million initiative dedicated to funding and advancing research to improve the lives of people living with bipolar disorder.
"This is a very ambitious project," said principal investigator Charles Lynch, an assistant professor of neuroscience in psychiatry at Weill Cornell Medicine. "It would be difficult to secure funding for a project of this scale from traditional funding sources. The grant from BD2 will allow us to quickly answer questions that otherwise would have taken a decade."
For many individuals living with Bipolar I Disorder, the path to stability is a profoundly challenging process of trial and error with existing medications, according to the investigators.
"The reality in the clinic is that even our best available treatments are not universally effective, and the burden of treatment side effects can substantially add to the disruptive illness itself," said co-principal investigator Dr. Immanuel Elbau, assistant professor of psychiatry and associate director of the Interventional Psychiatry Program at Weill Cornell Medicine.
"A major hurdle in clinical practice is the challenge of effectively treating depressive episodes without inadvertently triggering a switch into mania. This highlights a critical gap in our therapeutic arsenal and underscores the need for innovative approaches that can provide more targeted and sustainable relief, ultimately helping patients reclaim their lives from this illness," Elbau said.
Amy Kuceyeski, a professor of mathematics in neuroscience and radiology at Weill Cornell Medicine, is also part of the team, providing her expertise in imaging.
The project is using an innovative study design pioneered by Lynch and Dr. Conor Liston, M.D. '08, professor of psychiatry and of neuroscience in the Department of Psychiatry and the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine, to study patients with depression. Traditional clinical trials often follow hundreds of patients receiving a therapy or placebo and take a snapshot of their condition at select time points, such as 12 weeks or 6 months, but this may not capture the changing nature of symptoms in mood disorders. Instead, in the first prong of the project, Lynch and his colleagues will conduct weekly clinical assessments and brain scans on just five participants with bipolar disorder over the course of a year to identify the link between changes in brain circuits and symptoms.
The second prong of the project will be a clinical trial targeting these brain circuits with personalized transcranial magnetic stimulation. This therapy stimulates brain cells using magnetic fields and is used to treat individuals with mood disorders and other brain conditions. Lynch said they will map the unique brain anatomy of 62 patients with bipolar disorder and deliver individualized transcranial magnetic stimulation or a cross-over sham to determine whether targeting the circuits associated with mood shifts can stabilize patient's moods.
Stanford Medicine investigator Camarin Rolle will perform direct stimulation to brain circuits in patients with bipolar disorder who are already undergoing surgery for co-occurring epilepsy in the third prong in the study to confirm their role in mood state shifts.
"In a very short period of time, the project could help us to improve response rates to transcranial magnetic stimulation in people living with bipolar disorder," Lynch said. "Right now, the therapy is a one-size-fits-all approach, but this project will help us determine which circuits to target and how important it is to personalize treatment to an individual's unique brain anatomy."
Bridget Kuehn is a freelance writer for Weill Cornell Medicine.
