A pioneering £4.9 million research initiative is set to revolutionise our understanding of anergia - the crushing lack of energy that affects over 90% of people with depression and often lingers even after other symptoms subside.
Liam Mason, associate professor of clinical psychology at UCL, Annie Hata, lived experience expert and Jon Roiser, professor of neuroscience and mental health have received a five-year, Mental Health Award by the Wellcome Trust. Their goal is to uncover the brain circuits that make goals feel overwhelmingly effortful, and to design more personalised, targeted treatments for those affected.
While current treatments primarily target low mood or loss of pleasure, this ambitious project zeroes in on anergia’s neurocomputational roots: specifically, how the brain miscalculates effort and reward. Unlike anhedonia, which reflects a lack of enjoyment, anergia is defined by the overwhelming sense that effort simply isn’t worth it.
“This isn’t just tiredness,” says Dr Mason. “it’s a deeply embedded brain process that tells people the cost of effort is too high - and current treatments mostly miss it. By integrating insights from animal neuroscience, we believe we can shift the dial on how we understand anergia and develop new psychological interventions that target it.”
The international research team go after these questions across multiple species; and is led by collaborators at Washington University St Louis in the USA who are driving the animal neuroscience parts of the work, as well as world-leading clinical scientists at University of California Los Angeles. The project brings together human neuroimaging, computational modelling, and cutting-edge mouse neuroscience in a rare, bidirectional design that allows findings to inform both preclinical and clinical science.
Together, the team will identify the brain circuits and neurochemicals—like dopamine and glutamate—that shape how we perceive effort and reward, and may be at the root of anergia. The team will use artificial intelligence to identify different depression subtypes by looking at how their brains process effort, which could lead to more personalised treatments. They will also test whether these depression subtypes predict who benefits from therapy—and whether a new, effort-focused intervention can improve outcomes for those left behind by current treatments.
“We’re using state-of-the-art neuroimaging to pinpoint a brain region we think is central to how effort is evaluated,” explains Prof Roiser. “When this system goes awry during depression, people may struggle to engage in meaningful goals—not because they don’t care, but because their brain tells them it costs too much.”
The research is supported by an industry partner providing a novel smartphone app to track anergia in real-time, allowing researchers to follow effort-related decision-making in the context of everyday life.
Annie Hata, the study’s lived experience lead, will ensure the voices of people experiencing depression remain central throughout. “To make sure our research truly benefits the people it's meant to help, we're involving individuals with lived experience of mental health challenges at every stage. Co-production of science with the expertise of those with first-hand knowledge, we’re ensuring that our research is relevant, ethical, and practically applicable”
By linking cutting-edge neuroscience with clinical application, this study aims to reshape how we understand, identify, and treat one of depression’s most disabling symptoms—and bring renewed hope to millions worldwide.