An interdisciplinary team of researchers from the Departments of Psychiatry and Neurosurgery at Yale School of Medicine has launched a pioneering study aimed at uncovering the neural and genomic mechanisms that drive anxiety.
The five-year project is supported by a $5 million grant from the Wellcome Trust, a leading UK-based biomedical research funder. The research brings together psychiatry, neurosurgery, molecular neuroscience, and computational behavior sequencing to investigate the salience network—a brain circuit thought to underpin human emotional processing and threat perception.
Initial funding for pilot work came from the Yale Center for Brain & Mind Health and the Yale Kavli Institute. The project has already enrolled its first eight participants.
“This study creates the opportunity to have an unprecedented picture of the neural basis of human anxiety. We hope to leverage this information to create better predictive tests for anxiety problems like PTSD,” said John Krystal, MD, Robert L. McNeil, Jr. Professor of Translational Research and professor of psychiatry, of neuroscience, and of psychology, and chair of the Yale Department of Psychiatry.
The Wellcome-funded project, led by Krystal, will take an innovative cross-species approach to investigate the ways brain networks are synchronized to influence anxiety states. Eyiyemisi Damisah, MD, will record from the amygdalae and connected cortical structures in epilepsy patients undergoing neurosurgical monitoring to link specific patterns of neural activity to real-time measures of anxiety. In parallel, Alfred Kaye, MD, PhD, will use optogenetics and large-scale electrophysiology to experimentally understand emotional brain states in mice, allowing for causal tests of their behavioral impact.
Using advanced genetic approaches, Matthew Girgenti, PhD, will analyze the same brain networks to identify underlying mechanisms of anxiety-linked network activity. Robert Pietrzak, PhD, MPH will oversee the statistical components of the study, while Ilan Harpaz-Rotem, PhD, and Sarah Fineberg, MD, PhD, will support the clinical aspects.
By integrating molecular, circuit-level, and behavioral data across species, the team aims to define novel biomarkers and intervention targets for anxiety disorders. This groundbreaking work seeks to transform our understanding of anxiety and lay the foundation for targeted pharmacologic and neuromodulatory treatments.