Chronic fatigue linked to genes

Chronic fatigue syndrome, often dismissed as the imaginings of depressed and whiny people, is actually 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 (CDC).

Small changes in many of the genes in the brain prevent the nervous system from rebounding from everyday stress and less frequent, stronger insults, eventually triggering a cascade of responses that leaves the patient severely debilitated, researchers reported Thursday in 14 separate papers in the journal Pharmacogenomics.

"This is the first credible evidence for a biological basis" for the syndrome, said CDC director Dr. Julie Gerberding.

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.

The findings also are expected to lead to the development of effective treatments for patients, who now only receive therapy to mitigate symptoms, or in some cases, are scoffed at as slackers.

Chronic fatigue syndrome, or CFS, was recognized in the 1980s but was long dismissed as the complaint of "a bunch of hysterical, upper-class white women," said Dr. William Reeves of the CDC, who was a co-leader on the new study.

Diagnosis is difficult because many of the psychological symptoms, in mild form, are common traits of the modern stressful life.

In the intervening years, most physicians have come to recognize CFS as a valid illness, he added, but there has been virtually no information about its causes and it has been difficult to provide a precise definition of the disorder.

Experts agree it affects up to 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.

"[People with CFS] are as impaired as people with multiple sclerosis or AIDS or who are undergoing chemotherapy for cancer," Reeves said. "They don't die, but they are severely debilitated."

In the current study, research teams found 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, while others were exceptionally debilitating.

All forms, however, shared genetic mutations — technically called single nucleotide polymorphisms — related to brain activity that mediates 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 percent of cases.

The teams also found a strong correlation between the severity of CFS and what they called allostatic load, the cumulative wear and tear on the body resulting from chronic or inadequate adaptation to stresses, such as changes in everyday routine, disease and physical or emotional trauma.

The CDC is gearing up to attempt to replicate the findings in a study of 30,000 people in Georgia, Reeves said.