Marco Pignatelli, MD, an assistant professor of psychiatry at Washington University School of Medicine in St. Louis, has received a five-year $6.5 million grant from the Wellcome Trust to unravel little-known brain functions involved in depression. His project focuses on understanding the neurobiology underlying chronic anergia, the debilitating loss of energy and enthusiasm that affects 90% of people with depression.
“Anergia can be defined as the experience of profound low energy, even without exertion, with reduced propensity to expend effort leading to the avoidance of rewarding activities,” Pignatelli said. “It can have a severe impact on quality of life and is difficult to treat. We need to understand the cause to help guide the development of better therapies.”
The Wellcome grant will support the work of a multidisciplinary research team led by Pignatelli’s lab at WashU Medicine and including colleagues from University College London (UCL) and the University of California, Los Angeles (UCLA).
The project is designed to create a continuous feedback loop between researchers studying anergia in the lab and those working to apply and test new findings in clinical practice, according to Federica Lucantonio, PhD, an assistant professor of psychiatry at WashU Medicine and a co-leader of the study. “The research is intended to precisely measure the neural mechanisms underlying anergia so that these parameters can be used to better diagnose and group patients based on the specific factors contributing to their depression and the treatments most likely to benefit them,” Lucantonio said.
The Wellcome Trust, a global charitable foundation dedicated to improving health, is the United Kingdom’s largest independent funder of medical research. According to Wellcome, Pignatelli’s grant marks the first time that WashU Medicine will lead a major research study funded by the foundation.
Research by Pignatelli and colleagues suggests the root causes of anergia can be traced to a breakdown in communication among cells that form the basis of the brain’s motivation and reward system. For this study, his lab will use mouse models that mimic fundamental aspects of anergia to better understand how the disorder is influenced by the transmission of dopamine and other cellular messages across synapses, the points of contact among neurons in the brain.
Using an interdisciplinary approach integrating electrophysiology, cell biology and genetics, his team will measure how, in the context of anergia, small changes in neural messaging at the molecular level translate into big changes in perception — making previously rewarding activities seem less so. For instance, mice with stress-induced depression may experience appetite loss or become less interested in wheel running.
Pignatelli’s mouse research will be shared with the Wellcome Centre for Human Neuroimaging at UCL, where collaborators will use brain imaging to investigate similar neural mechanisms in humans. The UCL and UCLA teams will incorporate the new understanding of this neurobiology into the development of novel clinical approaches.
“By bridging the gap between basic neuroscience research and clinical application, our study aims to revolutionize the treatment landscape for depression, offering hope to millions worldwide,” Pignatelli said. “Over the next five years, we’ll characterize the computational, behavioral and neural circuit mechanisms that go awry in anergia and use this knowledge to develop clinical applications that specifically correct dysfunction in these mechanisms.”
About Washington University School of Medicine
WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,900 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 56% in the last seven years. Together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,900 faculty physicians practicing at 130 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.
Originally published on the WashU Medicine website
