Chronic fatigue syndrome, often dismissed as the imaginings of depressed and whiny people, is caused by genetic mutations that impair the central nervous system’s ability to adapt to stressful situations, according to a major new study by the Centers for Disease Control and Prevention.
Small changes in many of the genes in the brain prevent the nervous system from rebounding from everyday stress and from less frequent, stronger pressures, eventually triggering a cascade of molecular responses that leave the patient severely debilitated, researchers reported Thursday in 14 separate papers in the journal Pharmacogenomics.
The findings will provide immediate help in diagnosing the disorder, which often puzzles physicians because of the broad spectrum of symptoms and the absence of defining biochemical markers.
It should also lead to the development of effective treatments for patients, who receive only therapy to mitigate symptoms — or in some cases are scoffed at as slackers.
“It is very hard to treat an illness until you understand what it is physiologically,” said Dr. Lucinda Bateman of the Fatigue Consultation Clinic in Salt Lake City. “This is a very important foundation” for developing new treatments.
Chronic fatigue syndrome, commonly known as CFS, was first recognized in the 1980s but was long dismissed as the complaint of “a bunch of hysterical, upper-class white women,” said Dr. William C. Reeves of the CDC, who led the new study.
Diagnosis is difficult because many of the psychological symptoms, in mild form, are common traits of a modern stressful life.
Over the last two decades, most physicians have come to recognize CFS as a valid illness, he added, but there has been virtually no information about its causes. It has even been difficult to provide a precise definition of the disorder.
Experts agree that it affects as many as 1 million Americans, causing severe exhaustion, widespread musculoskeletal pain, impairments in thinking and sleep disturbances.
It strikes four times as many women as men but is equally debilitating in both. It occurs most frequently between the ages of 40 to 60.
Physiological manifestations, which must be present for at least six months for a diagnosis, can include sore throat, tender lymph nodes, headaches of a new or different type from those experienced in the past, and malaise after exertion.
The teams found that there were at least four distinct forms of the disease, each with its own genetic profile and symptoms but all including disabling fatigue. Some had relatively mild symptoms, whereas others were debilitating.
But all the forms shared genetic mutations — technically called single nucleotide polymorphisms — related to brain activity that mediated the response to stress.
In particular, five polymorphisms in three genes were “very important,” said Dr. Suzanne Vernon of the CDC, co-leader of the study. Those polymorphisms alone were sufficient to diagnose about 75% of cases.