Genetics puts tighter focus on chronic fatigue

Washington -- People who have chronic fatigue syndrome have a genetic makeup that hinders the body's ability to adapt to change, whether from infection, injury or other stressors, according to an interdisciplinary group of researchers who examined this puzzling and debilitating disorder.

The new findings were released by the Centers for Disease Control and Prevention in a series of papers that were published in the April issue of Pharmacogenomics.

Estimates suggest that more than 1 million people in the United States have the notoriously difficult to diagnose and treat CFS. Its symptoms, which include long-lasting bouts of fatigue, can result in about $20,000 in lost wages per family per year. The condition occurs most frequently in women ages 40 to 60 and can be as disabling as multiple sclerosis and chronic obstructive pulmonary disease, according to the CDC.

"For the first time ever, we have documented that people with CFS have certain genes that are related to those parts of brain activity that mediate the stress response," said William Reeves, MD, who heads the CDC's public health research program on the disorder.

It is hoped that the findings will provide a focus for researchers in pursuit of diagnostic tools and more effective treatments, he said.

In reaching their conclusions, CDC scientists and outside experts in medicine, molecular biology, epidemiology, genomics, mathematics, engineering and physics analyzed data from 227 CFS patients who volunteered to spend two days in the hospital. This information included measures of sleep physiology, cognitive function, autonomic nervous system function and such blood evaluations as an assessment of the activity of 20,000 genes. Overall, their work was directed at identifying factors that potentially cause or are related to CFS.

The research "reflects a remarkable confluence of a number of scientific advances coming to bear on a problem of great importance to people around the United States and one that's had controversies in the past," said CDC Director Julie Gerberding, MD, MPH, during a briefing on the studies.

The interdisciplinary nature of the research also represents a breakthrough, she said. "This approach is likely to work on a number of other vexing public health challenges."

As an example, she pointed to autism. With this condition, "again there is an unexplained appearance of a disease in the population and there is a growing hypothesis, at least, that an underlying genomic basis may set the foundation for other potential environmental events that trigger [its] expression."

In a move to pull together resources that focus on the genomic basis for disease, the CDC has developed a new Office of Public Health Genomics, she added.

Greater recognition

The hope among CFS patient advocates is that the CDC's time and attention will increase the disease's recognition. "Most lay people and a lot of health care workers don't take it seriously," said Leonard E. Jason, PhD, professor of psychology at DePaul University in Chicago.

Patients often have multiple symptoms, such as impairment in short-term memory or concentration, sore throat, muscle pain, headaches and sleep problems. With time in short supply, patients and physicians are unable to make much treatment progress. "Health care workers tend to say this is a psychiatric problem," Dr. Jason said.

"My own research has reported that about 90% of patients have never been adequately diagnosed," he said. "When the CDC comes out with findings that say there is a condition [that] occurs most frequently in women ages 40 to 60 and people take notice, I think that is in the public good."

Susan Levine, MD, an infectious diseases physician who treats CFS patients in New York City, also thought the study was a positive undertaking. "It underlines the complexities."

Particularly striking is the finding that an array of genes appears to be involved and that the researchers were able to distinguish individuals who become ill after an infectious disease from those who present with the illness after a stressful event, she said. "So it's interesting we have this marriage of genetic susceptibility and environmental factors."

Although an effective therapy for CFS is still in the future, the findings could spark the realization among physicians that the disorder is complex and more serious than they had previously thought, she added.

The studies also could inspire physicians to work as members of a multidisciplinary team for the sake of the patient rather than just sticking to their own specialty, Dr. Levine said. "Hopefully everyone will use their expertise in terms of giving the patients a worthwhile therapy."

She also serves on a committee that is trying to change the name of the condition. The thought is that the name might have something to do with the credibility problem. "When you say CFS, people kind of roll their eyes," Dr. Levine said. Often, it's because many people think they also are subject to bouts of fatigue. In England, for instance, CFS is myalgic encephalitis.

Meanwhile, among new names suggested in this county: chronic immune endocrine dysfunction syndrome or, her favorite, Osler's illness, named for William Osler, MD, a 19th-century Canadian physician highly regarded for blending the science of medicine with the art of healing.