Researchers from the Mark and Mary Stevens Neuroimaging and Informatics Institute ( Stevens INI ) at the Keck School of Medicine of USC are part of a new team studying the cellular, molecular, and neuroimaging signatures of a key brain region thought to contribute to mood switching between depression and mania, which are hallmark features of bipolar disorder.
The project is one of three recently funded Discovery Research grants from Breakthrough Discoveries for thriving with Bipolar Disorder (BD²), a nonprofit that funds bipolar disorder research. Each team will receive $4.5 million over three years. Christopher R.K. Ching, PhD , an assistant professor of research neurology at the Stevens INI, will share the award with fellow co-principal investigators Laramie Duncan, PhD, of Stanford University, and Fernando Goes, MD, of Johns Hopkins University.
Nearly 3% of people worldwide live with bipolar disorder, a chronic mental illness marked by manic and depressive mood switching. Scientists still know little about the biological mechanisms driving these mood episodes, making it challenging to diagnose and treat those with the disorder. The aim of the project is to reveal insights on those mechanisms that could eventually lead to new ways to treat the disorder.
The retrosplenial cortex sits toward the back of the brain and supports a wide range of cognitive functions, including memory and navigation. When damaged, it can lead to dissociation, a feeling of being detached from oneself or one’s surroundings.
In a 2025 study in Nature Neuroscience , Duncan and colleagues found that neurons in the retrosplenial cortex were strongly associated with bipolar disorder. The team calls these neurons “retrosplenial switch cells” and hypothesizes that they are essential for psychiatric health and that dysfunction in these cells contributes to mood switching. The new project will test that idea using novel cellular, genetic, and neuroimaging data.
The team will pursue three complementary lines of research. First, using molecular labeling, the researchers will compare cell types in the retrosplenial cortex of donated brain tissue from people with and without bipolar disorder to pinpoint which cells in this region differ in the disorder.
Second, drawing on the BD² Integrated Network, a long-term study recruiting 4,000 individuals with bipolar disorder, the team will test whether an individual’s genetic risk score can help predict mood switching and treatment response. A genetic risk score combines many subtle genetic risk markers into a single estimate of a person’s inherited likelihood of developing a condition or responding to a medication.
Third, the team will analyze brain scans from the large BD 2 cohort to examine how the retrosplenial cortex connects and communicates with other brain regions in people with bipolar disorder. Ching leads the ENIGMA Bipolar Disorder Working Group , a global effort of more than 250 researchers pooling brain imaging and clinical data to study the disorder.
“We will apply some of the cutting-edge structural and functional brain network modeling approaches we have developed in our large, international ENIGMA Bipolar group studies,” said Melody Kang, a USC Neuroscience PhD student working on the project.
“This is the type of ambitious, multidisciplinary project that would have been difficult to fund through traditional scientific grants,” Ching said. “This BD 2 project gives us a rare opportunity to link the changes we observe in the retrosplenial cortex at the human neuroimaging level to the underlying cellular and genetic factors that may lead to more clinically actionable markers aimed at improving diagnosis and treatment of bipolar disorder.”
The project is early-stage discovery research and does not test specific treatments. The team expects it to clarify which brain regions and cell types underlie mood switching and to identify molecular differences between people with and without bipolar disorder that could point to targets for future therapies.
“Mood switching shapes daily life for people with bipolar disorder, yet its biology remains poorly understood,” said Arthur W. Toga, PhD , director of the Stevens INI. “This project brings imaging, genetics, and cell biology together to address a single question, using data openly shared across research teams. That combination gives us a much better chance of finding answers that matter to patients.”
The project, “ Retrosplenial Cortex ‘Switch Cells’ in Bipolar Disorder ,” is funded by a BD² Discovery Research grant. With this round, BD² has committed more than $119 million to bipolar disorder research.