Hidden Energy Imbalance in Brain Cells May Play a Role in Early Depression
Researchers may have uncovered a promising new way to detect and treat major depression at an earlier stage, which could improve recovery prospects for many patients.
Scientists at the University of Queensland, working with colleagues at the University of Minnesota, investigated levels of adenosine triphosphate (ATP)—often described as the body’s “energy currency”—in the brains and blood cells of young adults diagnosed with major depressive disorder (MDD).
Associate Professor Susannah Tye from the University of Queensland’s Queensland Brain Institute said the results are the first to identify matching patterns in these energy-related molecules in both the brain and bloodstream of young people with MDD. The findings suggest that some depression symptoms may be tied to basic changes in how brain and blood cells manage energy.
Fatigue is one of the most common and difficult-to-treat symptoms of MDD, and finding an effective treatment can take years. The researchers hope that a better understanding of the biology behind fatigue and other symptoms could support earlier intervention and more targeted therapies.
Brain Scans and Blood Samples
For the study, a team at the University of Minnesota collected brain imaging data and blood samples from 18 participants aged 18 to 25 who had been diagnosed with MDD. Researchers at the Queensland Brain Institute then analyzed those samples and compared them with samples from people without depression.
An Unexpected Energy Signature
Queensland Brain Institute researcher Dr. Roger Varela said the team observed an unusual pattern in cells from participants with depression. Their cells appeared to produce higher levels of energy-related molecules while at rest, but they had difficulty increasing energy production when under stress.
According to the researchers, this may indicate that cells are “overworking” early in the illness, potentially leading to longer-term strain. The pattern was unexpected, as lower energy production might be assumed in depression. Instead, the findings point to a reduced ability—particularly in mitochondria, the cell’s energy-producing structures—to meet higher energy demand in the early stages of depression. This reduced capacity could contribute to low mood, decreased motivation, and slower cognitive function.
Implications for Stigma and Treatment
Dr. Varela said the results may also reshape how depression is understood by highlighting that measurable biological changes can occur throughout the body, including in the brain and blood, and that depression can affect energy regulation at a cellular level.
The researchers also emphasize that depression is not a single, uniform condition. Individuals may have different underlying biology, meaning they can be affected in different ways and may respond differently to treatment. The team hopes the work will help guide the development of more specific and effective treatment options.
The study was led by Dr. Katie Cullen at the University of Minnesota. The brain imaging technique used to measure ATP production was developed by Professors Xiao Hong Zhu and Wei Chen. The research was published in Translational Psychiatry.
