Scientific Frontline: "At a Glance" Summary: Cellular Changes in Depression-Related Fatigue
- Main Discovery: Patterns of adenosine triphosphate molecules are altered in the brain and bloodstream of young people with major depressive disorder, demonstrating that depression symptoms are rooted in fundamental changes to cellular energy utilization.
- Methodology: Researchers gathered blood samples and brain scans to analyze adenosine triphosphate levels in young adults diagnosed with major depressive disorder, comparing the molecular data against control samples from participants without depression.
- Key Data: Blood samples and brain scans from 18 individuals aged 18 to 25 years revealed that cells in depressed patients produced excess energy molecules while resting, but possessed a significantly reduced capacity to increase energy production under physiological stress.
- Significance: The inability of cellular mitochondria to cope with elevated energy demands early in the illness provides a concrete biological mechanism for clinical symptoms such as severe fatigue, low mood, reduced motivation, and slower cognitive function.
- Future Application: Identifying these cellular energy deficiencies establishes novel biomarkers that will facilitate early clinical diagnosis, reduce social stigma by proving a physical pathogenesis, and drive the development of highly targeted therapeutic interventions.
- Branch of Science: Neuroscience, Psychiatry, and Cellular Biology.
Researchers may have discovered a new way to diagnose and treat major depression at the earliest stage of the condition, giving patients the best opportunity for recovery.
University of Queensland researchers, in collaboration with the University of Minnesota, 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 this was the first time patterns in these fatigue molecules had been discovered in both the brain and blood stream 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.”
During the study, a team at the University of Minnesota collected blood samples and scans from 18 people aged 18-25 years, who had been diagnosed with MDD.
These were then analysed by the QBI team and compared with samples from participants who did not have depression.
QBI researcher Dr Roger Varela said they found cells in people with depression produced more energy molecules when resting, but had a reduced ability to increase energy production under 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.”
Dr Varela hopes this 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,” 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.”
Title: ATP bioenergetics and fatigue in young adults with and without major depression
Authors: 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
Source/Credit: University of Queensland
Reference Number: psy031126_02