Depression impacts energy at a cellular level, researchers find

Depression symptoms may be rooted in fundamental changes in the way brain and blood cells use energy, a team of researchers from the University of Queensland (UQ), in collaboration with the University of Minnesota, has revealed.

For the study, published open access in Translational Psychiatry (doi.org/10.1038/s41398-026-03904-y), the team analysed levels of adenosine triphosphate (ATP) — known as the ‘energy currency’ molecule — in the brain and blood cells of young people with depression.

Associate Professor Susannah Tye from UQ’s Queensland Brain Institute (QBI) said it was the first time patterns in these fatigue molecules had been discovered 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,” 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,” Tye added. “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.”

The team at the University of Minnesota collected blood samples and scans from 18 people aged 18–25 years who had been diagnosed with MDD. The QBI team then analysed these and compared them with samples from participants who did not have depression.

They found cells in people with depression produced more energy molecules when resting, but had a reduced ability to increase energy production under stress, QBI researcher Dr Roger Varela said.

“This suggests cells may be overworking early in the illness, which could lead to longer-term problems,” 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.”

Varela said he hopes the research will help de-stigmatise 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,” Varela 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,” Varela concluded.

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