A new study reveals distinct molecular mechanisms underlying two long-misunderstood brain disorders: chronic fatigue syndrome (CFS) and Gulf War Illness (GWI). These two illnesses, which were long thought to be psychological in nature, share significant commonalities such as pain, fatigue, cognitive dysfunction, and exhaustion after exercise.
The new study by researchers at Georgetown University Medical Center (GUMC) draws on previous findings from the team regarding two GWI subtypes. Their study lays the groundwork needed to understand these disorders in order to diagnosis and treat them effectively.
The changes in brain chemistry were observed in levels of microRNA (miRNA) — small non-coding RNA molecules that turn protein production on or off — 24 hours after riding a stationary bike for 25 minutes.
“We clearly see three different patterns in the brain’s production of these molecules in the CFS group and the two GWI phenotypes,” said senior investigator James N. Baraniuk, M.D., professor of medicine at Georgetown University School of Medicine.
“This news will be well received by patients who suffer from these disorders who are misdiagnosed and instead may be treated for depression or other mental disorders.”
Baraniuk worked on the study with Narayan Shivapurkar, Ph.D., assistant professor of oncology at the medical school.
Chronic fatigue syndrome affects between 836,000 and 2.5 million Americans, according to a National Academy of Medicine report. The condition was believed by some to be psychosomatic until a 2015 review of 9,000 articles over 64 years of research pointed to unspecified biological causes. Still, no definitive diagnosis or treatment is available.
Many Gulf War veterans were exposed to a combination of nerve agents, pesticides, and other toxic chemicals that may have triggered the chronic pain, cognitive, gastrointestinal, and other problems, Baraniuk says. The illness occurs in more than one-fourth of the 697,000 veterans deployed to the 1990-1991 Persian Gulf War, according to earlier work by the research team.
Although the mechanisms behind GWI remain unknown, the new findings provide significant insights into brain chemistry that can now be investigated.
For the study, the researchers focused on spinal fluid of CFS, GWI and control subjects who agreed to have a lumbar puncture. Before exercising, miRNA levels were the same across all participants; however, after exercising, significant differences were found.
The CFS, control and two subtypes of GWI groups had distinct patterns of change. For example, CFS patients who exercised had reduced levels of 12 different mRNAs, compared to those who did not exercise.
In addition to the exercise-related miRNA changes in the two GWI subtypes, one subgroup also developed jumps in heart rate of over 30 beats when standing up that lasted for two to three days after exercise. Magnetic resonance imaging (MRI) showed that these patients had smaller brainstems in regions that control heart rate and which did not activate their brains while doing a cognitive task.
In contrast, the other GWI subgroup did not show any heart rate or brainstem changes, but their brains needed to recruit additional regions to complete a memory test. The two groups were as different from each other as they were from the control group.
Finding two distinct pathophysiological miRNA brain patterns in patients reporting Gulf War disease “adds another layer of evidence to support neuropathology in the two different manifestations of Gulf War disease,” says Baraniuk.
He adds that miRNA levels in these disorders were different from the ones that are altered in depression, fibromyalgia, and Alzheimer’s disease, further suggesting CFS and GWI are distinct diseases.
The new findings are published in the journal Scientific Reports.