BD² Awards over $13 Million in Grants to Understand the Mechanisms of Mood State Switching in Bipolar Disorder and Announces New Funding Available

Highlights:

• Understanding Mood State Switching: Three new BD² Discovery Research teams will explore how external risk factors trigger manic or depressive episodes.
• New Insights: Research led by scientists and clinicians at Harvard Medical School, Johns Hopkins University, and Stanford University will offer new insights and potential treatments for people with bipolar disorder.
• New Funding Announced: A new RFA for Discovery Research focused on women’s health is now taking applications, with up to $5 million available per grant.

Washington, DC — Breakthrough Discoveries for thriving with Bipolar Disorder (BD²) today announced its fourth round of Discovery Research grants, totaling more than $13 million, focused on the biological mechanisms of intense mood changes, a hallmark of bipolar disorder. Each of the three teams, led by researchers from Harvard Medical School, Johns Hopkins University, and Stanford University, will receive $4.5 million over three years, joining current Discovery Research grantees in pursuing innovative research that deepens our understanding of bipolar disorder and paves the way for improved treatment.

Nearly 3% of the global population lives with bipolar disorder, and the vast majority experience mood state switching, sudden transitions between opposing emotional states such as depression and mania. However, little is known about the biological mechanisms that drive these switches, or how external stressors trigger them. This new cohort of grantees will work to close that gap, exploring how factors like substance use, molecular signaling, or seasonal changes can bring on manic or depressive episodes. Two of these teams will have formal collaborations with the BD² Integrated Network, the longitudinal cohort study that will accelerate findings and connect the research to real-world settings.

The three grantee teams are approaching mood state switching from different biological angles, building a complementary understanding of what drives mood switching episodes.

• Laramie Duncan, PhD, of Stanford University leads a team that recently found that a rare neuron type in an understudied brain region, the retrosplenial cortex, is strongly linked to bipolar disorder. The team will now study how this cell type contributes to mood switching. They will also draw on BD²’s longitudinal cohort of over 600 people with bipolar disorder to test whether genetic risk can help match patients to treatments, and use brain imaging to assess changes in retrosplenial cortex connectivity.
• Susan Dymecki, MD, PhD, of Harvard Medical School leads a team that recently identified a neural circuit linking the brain’s master circadian clock to mood and arousal centers, which shifts its signaling in response to changes in light exposure. People with bipolar disorder are highly sensitive to changes in day length, jet lag, and nighttime screen exposure — all of which can trigger mood-switch episodes. The team will now test whether dysfunction in this neural circuit drives light-triggered mood episodes, and whether targeting it could help stabilize mood.
• Akira Sawa, MD, of Johns Hopkins University leads a team that will study how potassium and calcium channels, which are critical to neural activity, interact, and how abnormal changes in that interaction may disrupt signaling and drive mood switching. Combining cell-based models, animal studies, nasal biopsy-based human primary neurons, and data from the first data release of BD²’s longitudinal cohort of over 600 people with bipolar disorder, the team will test this mechanism as a potential treatment target and biomarker for diagnosis.

Learn more about the projects and teams.

“Understanding why and how mood states switch is essential to developing more precise, effective treatments, and we’re proud to support this work as part of our long-term commitment to helping people with bipolar disorder lead thriving lives,” said Daniel Pham, PhD, Head of Science and Innovation at BD².

With these new grants, BD² has now committed over $119 million to research that accelerates scientific understanding of bipolar disorder and advances clinical care through cross-disciplinary collaboration, data sharing, and real-time learning. This fourth round of Discovery Research builds on previous grantees’ work studying the genetic risk factors of bipolar disorder, the molecular and circuit-level mechanisms underlying sleep disruption, and mechanisms of action for drug-based therapies — together forming a growing portfolio of insight into bipolar disorder.

BD² has since opened a fifth round of funding, inviting teams to apply for up to $5 million per grant, with a spotlight on women’s health and connections into the Integrated Network. Additionally, new cycle teams will have up to $5 million in funding over four years — an expansion from previous cycles aimed at giving successful teams more time and resources to increase their scientific impact, meeting the community’s need for greater funding and long-term stability. More on the request for applications here.