Marco Pignatelli, MD, an assistant professor in psychiatry at Washington University School of Medicine in St. Louis, has been awarded a five-year $6.5 million grant from the Wellcome Trust to explore obscure brain functions associated with depression. His initiative aims to comprehend the neurobiology related to chronic anergia, the debilitating lack of energy and enthusiasm that impacts 90% of individuals with depression.
“Anergia can be described as experiencing profoundly low energy, even without physical effort, resulting in a diminished tendency to engage in activities that were once rewarding,” Pignatelli explained. “This condition can severely affect one’s quality of life and is challenging to treat. We must understand the underlying cause to inform the development of more effective therapies.”
The Wellcome grant will facilitate the endeavors of a multidisciplinary research team guided by Pignatelli’s lab at WashU Medicine, which includes collaborators from University College London (UCL) and the University of California, Los Angeles (UCLA).
The initiative is structured to establish a continuous feedback mechanism between researchers investigating anergia in the laboratory and those applying and validating new discoveries in clinical settings, as indicated by Federica Lucantonio, PhD, an assistant professor in psychiatry at WashU Medicine and a co-leader of the project. “The aim of the research is to accurately assess the neural mechanisms associated with anergia so that these elements can aid in better diagnosing and categorizing patients based on the specific factors affecting their depression and the treatments that are most likely to be beneficial,” Lucantonio noted.
The Wellcome Trust, a worldwide charitable organization focused on enhancing health, is the largest independent financier of medical research in the United Kingdom. Pignatelli’s grant signifies the first occasion that WashU Medicine will spearhead a significant research initiative funded by the foundation, according to Wellcome.
Investigations by Pignatelli and associates indicate that the underlying causes of anergia may be linked to disruptions in communication among cells that constitute the foundation of the brain’s motivation and reward systems. For this research, his laboratory will employ mouse models that replicate fundamental characteristics of anergia to deepen the understanding of how the disorder is impacted by the transfer of dopamine and other cellular signals across synapses, the contact points between neurons in the brain.
By utilizing an interdisciplinary strategy that includes electrophysiology, cell biology, and genetics, his group will evaluate how, within the context of anergia, minor alterations in neural signaling at the molecular level can lead to significant shifts in perception — making previously gratifying activities appear less appealing. For example, mice experiencing depression due to stress may suffer from a decrease in appetite or show less interest in running on wheels.
Pignatelli’s mouse studies will be shared with the Wellcome Centre for Human Neuroimaging at UCL, where partners will utilize brain imaging techniques to explore similar neural mechanisms in humans. The UCL and UCLA teams will integrate the newfound insights into neurobiology into the creation of innovative clinical strategies.
“Our study, aiming to bridge the divide between fundamental neuroscience research and clinical application, seeks to transform the treatment paradigm for depression, providing hope to millions globally,” Pignatelli stated. “In the upcoming five years, we will define the computational, behavioral, and neural circuit mechanisms that malfunction in anergia and leverage this understanding to formulate clinical applications that specifically rectify dysfunction in these mechanisms.”
About Washington University School of Medicine
WashU Medicine is a leading figure in academic medicine, encompassing biomedical research, patient care, and educational programs with a faculty of 2,900. Its portfolio of National Institutes of Health (NIH) funding is the second largest among U.S. medical schools and has expanded by 56% over the past seven years. Alongside institutional investments, WashU Medicine allocates over $1 billion annually to basic and clinical research innovation and education. Its faculty practice consistently ranks within the top five nationally, with over 1,900 faculty physicians practicing across 130 locations, who also serve as the medical staff of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine boasts a rich history in MD/PhD training, having recently committed $100 million towards scholarships and curriculum improvements for its medical students, while also housing premier training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communication sciences.
Initially published on the WashU Medicine website
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