Researchers at Georgetown University Medical Center have found distinct molecular signatures in two brain disorders long thought to be psychological in origin—chronic fatigue syndrome (CFS) and Gulf War Illness (GWI). The disorders share commonalities, such as pain, fatigue, cognitive dysfunction, and exhaustion after exercise.
“This news will be well received by patients who are misdiagnosed and instead may be treated for depression or other mental disorders,” says James N. Baraniuk, MD, professor of medicine and senior investigator on this study. Narayan Shivapurkar, PhD, assistant professor of oncology at the medical school, was also a member of the research team.
The work supports a previous observation by Georgetown investigators that there are two variants of GWI. GWI has developed in more than one-fourth of the 697,000 veterans deployed to the 1990-1991 Persian Gulf War, according to Baraniuk and his colleagues.
CFS affects between 836,000 to 2.5 million Americans, according to a National Academy of Medicine report. The disorder was thought to be psychosomatic until a 2015 review of 9,000 articles, spanning 64 years of research, pointed to unspecified biological causes. No definitive diagnosis or treatment is currently available.
This study focused on spinal fluid of CFS, GWI, and control subjects. Spinal taps before exercise showed miRNA levels were the same in all participants. In contrast, they were significantly different after exercise, with each study group showing distinct patterns of change. For example, CFS subjects who exercised had reduced levels of 12 different mRNAs, compared to those who did not exercise.
The two GWI subtypes showed other differences caused by exercise. One subgroup developed jumps in heart rate of over 30 beats when standing up that lasted for two to three days after exercise. Imaging showed they had smaller brainstems in regions that control heart rate, and did not activate their brains when doing a cognitive task. In contrast, the other subgroup did not have any heart rate or brainstem changes, but did recruit additional brain regions to complete a memory test. According to Baraniuk, finding two distinct pathophysiological brain patterns in patients reporting GWI “adds another layer of evidence to support neuropathology in the two different manifestations of Gulf War disease.”
The study lays the groundwork to understand each of these disorders in order to diagnose and treat them effectively, says Baraniuk.