Chronic fatigue sufferers are often treated with skepticism and occasionally derision. Because their symptoms are so diffuse and because it has been difficult to pin down clear markers of the disease or its sources, many see chronic fatigue syndrome (CFS) as in the mind of the afflicted person.

A new study, however, which finds clear changes in their blood chemistry may help change that. The study also reports evidence of distinct stages of the disease.

The changes were seen in cytokines, tiny proteins and peptides that are similar to hormones and often affect the immune system. Levels of several cytokines, most notably interferon gamma, and others including interleukin-17A, were elevated in patients who had the disease for three years or less. Cytokine levels did not change in those who had the disease longer or in people who were not sick, evidence that there are different stages to the disease.

We now have evidence confirming what millions of people with this disease already know, that ME/CFS isn't psychological.

Chronic fatigue syndrome goes by a variety of names, including myalgic encephalitis (ME) and systemic exertion intolerance disease. Sometimes it's simply called chronic fatigue.

“It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop,” said lead author Mady Hornig in a statement.

The findings suggest that in chronic fatigue sufferers, something causes an activation of the immune system, an activation that persists for about three years. And while the results don't point to what caused this activation, they do suggest some potential treatments.

Antibodies that lower the amount of interleukin-17A are already on the market. But before any drugs are likely to be tested in a clinical trial, the researchers plan to conduct a time-based study that follows patients for a year, both to confirm their results and to see how cytokine levels change and differ within individual patients over time.

“We now have evidence confirming what millions of people with this disease already know, that ME/CFS isn't psychological,” Hornig, a professor at Columbia University’s Mailman School of Public Health, said. “Our results should accelerate the process of establishing the diagnosis after individuals first fall ill, as well as discovery of new treatment strategies focusing on these early blood markers.”

In the study, published in Science Advances, researchers looked at levels of 51 different blood compounds in 298 chronic fatigue patients and 348 healthy controls, and found distinct patterns present in the blood of short-term chronic fatigue sufferers.

Brain scans of CFS suffers offer more evidence that something real is going on. Researchers at Stanford University found that brains of chronic fatigue patients have less white matter, abnormalities in a specific nerve tract in the right hemisphere of the brain called the right arcuate fasciculus (RAF), and a thickening of the gray matter in the two areas of the brain that the RAF connects.

The Stanford team also noted a fairly strong correlation between the degree of abnormality in a CFS patient's right arcuate fasciculus and the severity of the patient's condition.

Taken together, the two studies present evidence that chronic fatigue is a physical illness, not a psychological disturbance or a state of mind.