Researchers have found differences in the brains and immune systems of people who have chronic fatigue syndrome after an infection.
According to the researchers, the findings, for the first time, suggest a link between specific abnormalities or imbalances in the brain and post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS).
They also found distinct differences between men and women with the condition.
Symptoms of the condition include extreme tiredness, problems sleeping and difficulty concentrating.
It can affect anyone, including children, but is more common in women, and tends to develop between the mid-20s and mid-40s.
It is not known what causes ME/CFS, but the new study indicates that rather than physical exhaustion or a lack of motivation, fatigue may arise from a mismatch between what someone thinks they can achieve and what their bodies perform.
Scans revealed that people with ME/CFS had lower activity in a region towards the back of the brain, which may cause fatigue by disrupting the way the brain decides how to exert effort.
Analysis of spinal fluid also found abnormally low levels of molecules that help regulate the nervous system in people with ME/CFS compared with healthy people.
Reduced levels of certain chemicals in the fluid were associated with worse movement, effort-related behaviour and cognitive symptoms.
Walter Koroshetz, director of the US’s the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS), said: “People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult.
“This in-depth study of a small group of people found a number of factors that likely contribute to their ME/CFS.
“Now researchers can test whether these findings apply to a larger patient group and move towards identifying treatments that target core drivers of the disease.”
People in the study, published in Nature Communications, were asked to make risk-based decisions about exerting physical effort.
The study found that those with ME/CFS had difficulties with the effort choice task and with sustaining effort.
A brain region in charge of telling the body to move also remained abnormally active during fatiguing tasks.
There were no signs of muscle fatigue, suggesting that fatigue in ME/CFS could be caused by a dysfunction of brain regions that drive movement of the body.
Dr Brian Walitt, associate research physician at NINDS and first author of the study, said: “We may have identified a physiological focal point for fatigue in this population.
“Rather than physical exhaustion or a lack of motivation, fatigue may arise from a mismatch between what someone thinks they can achieve and what their bodies perform.”
Researchers also discovered immune differences between men and women with the condition.
Avindra Nath, clinical director at NINDS and senior author of the study, said: “Men and women were quite divergent in their data, and that tells you that ME/CFS is not one-size-fits-all.
“Considering male and female immune differences in ME/CFS, the results may open up new avenues of research that could provide insight into other infection-associated chronic diseases.”
Immune testing revealed that people with ME/CFS had higher levels of certain cells that help the immune system fight off disease, compared with healthy people.
More studies are needed to determine how these immune markers relate to brain dysfunction and fatigue in ME/CFS.
The study took a comprehensive look at ME/CFS that developed after a viral or bacterial infection, using state-of-the-art techniques to examine 17 people with PI-ME/CFS who had been sick for less than five years, and 21 healthy people.
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