Researchers may have identified a potential new way to diagnose and treat major depression at its earliest stages, a development that could improve the chances of recovery for many patients.
Scientists Investigate Energy Molecules in Depression
Scientists at the University of Queensland worked with collaborators from the University of Minnesota to examine levels of adenosine triphosphate (ATP) – known as the “energy currency” molecule – in the brains and blood cells of young people diagnosed with depression.
Associate Professor Susannah Tye from UQ’s Queensland Brain Institute (QBI) said the study is the first to identify patterns in these fatigue-related molecules in both the brain and bloodstream of young people with major depressive disorder (MDD).
“This suggests that depression symptoms may be rooted in fundamental changes in the way brain and blood cells use energy,” Dr. Tye said.
“Fatigue is a common and hard-to-treat symptom of MDD, and it can take years for people to find the right treatment for the illness.
“There has been limited progress in developing new treatments because of a lack of research, and we hope this important breakthrough could potentially lead to early intervention and more targeted treatments.”
Study Examines Brain Scans and Blood Samples
For the study, researchers at the University of Minnesota gathered brain scans and blood samples from 18 participants between the ages of 18 and 25 who had been diagnosed with MDD.
The Queensland Brain Institute team then analyzed those samples and compared them with samples collected from individuals who did not have depression.
Unexpected Energy Patterns in Cells
QBI researcher Dr. Roger Varela said the team found that cells from people with depression produced higher levels of energy molecules while at rest, but struggled to boost energy production when faced with stress.
“This suggests cells may be overworking early in the illness, which could lead to longer-term problems,” Dr. Varela said.
“This was surprising, because you might expect energy production in cells would be lower for people with depression.
“It suggests that in the early stages of depression, the mitochondria in the brain and body have a reduced capacity to cope with higher energy demand, which may contribute to low mood, reduced motivation, and slower cognitive function.”
Toward Better Understanding and Treatment
Dr. Varela said he hopes the findings will also help reduce stigma surrounding depression.
“This shows multiple changes occur in the body, including in the brain and the blood, and that depression impacts energy at a cellular level,” he said.
“It also proves not all depression is the same; every patient has different biology, and each patient is impacted differently.
“We hope this research will help lead to more specific and effective treatment options.”
The study was led by the University of Minnesota’s Katie Cullen MD, and the imaging method used to measure ATP production in the brain was developed by Professors Xiao Hong Zhu and Wei Chen.
The research is published in Translational Psychiatry.
Reference: “ATP bioenergetics and fatigue in young adults with and without major depression” by Kathryn R. Cullen, Susannah J. Tye, Bonnie Klimes-Dougan, Hannes M. Wiesner, Roger B. Varela, Brooke Morath, Lin Zhang, Wei Chen and Xiao-Hong Zhu, 4 March 2026, Translational Psychiatry.
DOI: 10.1038/s41398-026-03904-y
Funding: NIH/National Institutes of Health, University of Minnesota
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