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Investigators Launch Study Aimed at Accelerating Understanding of Bipolar Disorder

September 19, 2023

A multidisciplinary team of researchers based at Yale will launch a series of studies aimed at accelerating understanding of bipolar disorder and generating new and more effective treatments.

Together with Harvard University, Stanford University, and the New York Genome Center, Yale will be one of four sites funded by $18 million in research grants from BD²: Breakthrough Discoveries for Thriving with Bipolar Disorder, a research funding initiative that brings together researchers, clinicians, philanthropists, and people with lived experience to study and treat bipolar disorder.

The unprecedented opportunities for researchers to perform this work in the context of the highly collaborative larger BD² network, we think, have potential to be transformative.

Hilary Blumberg, MD

Each site will receive grants of up to $4.5 million from the BD² Discovery Research program over three years to examine the fundamental mechanisms of bipolar disorder.

Yale’s research team will be led by Hilary Blumberg, MD, John and Hope Furth Professor of Psychiatric Neuroscience and Professor of Psychiatry, and in the Child Study Center and of Radiology and Biomedical Imaging. Blumberg directs Yale School of Medicine’s Mood Disorders Research Program; her research is devoted to understanding the brain circuitry differences that underlie mood disorders across the lifespan, with a focus on bipolar disorder and suicide prevention.

“The Discovery Research program is the cornerstone of BD²’s work to improve understanding so that we can more effectively diagnose and improve treatment for the tens of millions of people living with bipolar disorder,” said Cara Altimus, PhD, managing director for BD² and senior director at the Milken Institute. “These teams of scientists will work within their own institutions and collaborate across teams to explore hypotheses on the biological causes of bipolar disorder.”

Blumberg will lead her team to investigate the roles of mitochondria, the energy powerhouses of cells, in the brain in bipolar disorder and how they can lead to the low-energy symptoms of depression and high-energy symptoms of mania.

In a unique multidisciplinary effort, they will study mitochondria from their basic genetic and molecular mechanisms to how they change brain-cell metabolism and functioning, to how they affect brain-circuitry functioning and symptoms. These studies will expand knowledge about bipolar-disorder biology. Importantly, they will translate their findings into pharmacological therapeutics and behavioral interventions.

This work will be divided into four projects, or “aims;” each will have a unique focus and will contribute to Yale’s overall integrated multidisciplinary research approach.

Blumberg is both the project’s principal investigator and lead on Aim 1. Researchers in her group will perform extensive characterization of people with bipolar disorder, including details of clinical, behavioral, and psychosocial risk factors, and will use new multimodal brain-scanning methods to study brain-system function and metabolism.

In-Hyun Park, PhD, associate professor of genetics, will lead Aim 2 in which, from the blood samples of participants in Aim 1, he will generate and study stem cells and “brain organoids.” This will allow for study of each individual’s brain cell physiology and its response to specific treatments.

Aim 3’s intensive mitochondrial study will be led by Elizabeth Jonas, MD, Harvey and Kate Cushing Professor of Medicine, who was a discoverer of the mitochondrial mechanism that will be the focus of the work.

Hongying Shen, PhD, assistant professor of cellular and molecular physiology, will use state-of-the-art CRISPR methods to study mitochondrial genetic mechanisms in leading Aim 4. Other Yale scientists collaborating with in this study include Kristen Brennand, PhD; Todd Constable, PhD; Irina Esterlis, PhD; Joy Hirsch, PhD; and Graeme Mason, PhD, who will be joined by University College of London Professor in Biomedical Engineering Ilias Tachtsidis, PhD.

“This support from BD² will provide us unique opportunities to study the same individuals with bipolar disorder with new ways to scan their brains to examine brain-circuitry function and metabolism and, in brain cells derived with recent stem cell technologies from their blood samples, study individual genetic and molecular mechanisms involved and how they respond to specific medications,” Blumberg said. “The unprecedented opportunities for researchers to perform this work in the context of the highly collaborative larger BD² network, we think, have potential to be transformative in elucidating causes of BD and in generating more effective diagnostic and treatment methods.”

Submitted by Christopher Gardner on September 19, 2023