Study offers clues into chronic fatigue syndrome

US researchers have reported abnormalities in brain and immune system function which may explain the symptoms seen in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

An in-depth study comparing in 17 people with ME/CFS and 21 healthy volunteers also uncovered clear differences between men and women with the condition.

The research was welcomed by UK scientists as an important step towards understanding the biological basis for ME/CFS because it looked in so much detail at multiple systems in the body rather than focusing on one aspect.

One particularly interesting part of the study suggested that imbalances in the brain activity relate to feelings of fatigue.

The researchers used functional magnetic resonance imaging (fMRI) of the brain and found that people with ME/CFS had lower activity in the temporal-parietal junction, which may disrupt the way the brain decides how to exert effort leading to fatigue.

It appeared that the motor cortex also remained abnormally active during fatiguing tasks but there were no signs of muscle fatigue.

Participants were asked to make risk-based decisions about exerting physical effort and researchers found that those with ME/CFS had difficulties with the task.

The results prompted researchers to conclude that fatigue may arise from a mismatch between what someone thinks they can achieve and what their bodies do.

And it may all be driven by immune dysfunction, they reported in Nature Communications.

The ME/CFS group had higher levels of naive B cells and lower levels of switched memory B cells compared to healthy controls.

There was also abnormally low levels of catecholamines and other molecules that help regulate the nervous system in the spinal fluid of people with ME/CFS compared to healthy controls.

Reduced levels of certain catecholamines were associated with worse motor performance, effort-related behaviours, and cognitive symptoms, they added.

More studies will be needed to understand how immune markers relate to brain dysfunction and fatigue in ME/CFS, they said, but it could relate to a persistent immune response.

There were differences between men and women in gene expression patterns, immune cell populations, and metabolic markers as well as distinct markers of inflammation.

Study author Dr Avindra Nath, clinical director at of NIH’s National Institute of Neurological Disorders and Stroke (NINDS) said: ‘We think that the immune activation is affecting the brain in various ways, causing biochemical changes and downstream effects like motor, autonomic, and cardiorespiratory dysfunction.’

Co-author Dr Brian Walitt also from NINDS added: 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.’

Professor Karl Morten, principle investigator at the Nuffield Department of Women’s and Reproductive Health at the University of Oxford, said the results from the study would help researchers focus their efforts.

‘The brain appears to be potentially driving the patient response. The big question is why. Is something still going on we are not yet aware of.

‘The immune system is dysregulated and appears to still be showing an antigen response. Is this suggesting a foreign entity is still present or has the system gone rogue.’