By Judy Foreman
September 5, 2005

For years, many doctors and others dismissed people with Chronic Fatigue Syndrome as depressed, lazy, or just plain whiny.

Now, a slew of research -- more than 2,000 scientific papers by some counts -- is suggesting that chronic fatigue is not a psychiatric illness, but a nasty mix of immunological, neurological, and hormonal abnormalities.

Several types of brain scans, for instance, have found different patterns of blood flow to certain regions of the brain in patients with chronic fatigue, and other studies have shown that patients have difficulty in thinking and
processing information, and are unable to do several mental tasks at once.

''There are objective brain abnormalities in many patients with CFS that are consistent with the symptoms patients describe," said Dr. Anthony Komaroff, a chronic fatigue expert and editor-in-chief of Harvard's Health Publications, a division of Harvard Medical School.

Chronic fatigue, which has no known cure, is more than feeling tired all the time. Definitions vary, but the one the federal government uses says it is characterized by persistent, unexplained fatigue lasting at least six months, as well as four of the following: sore throat, tender lymph nodes, muscle pain, multi-joint pain, headaches, un-refreshing sleep, malaise after exercise, and impaired memory or concentration.

The syndrome -- which can come on after an acute infection, a head injury, a major life stress, or from no obvious triggers at all -- now affects 800,000 to 2.5 million Americans, most of them women, said Dr. William Reeves, chief of CFS research at the federal Centers for Disease Control and Prevention.

But the ailment is tricky to diagnose because its symptoms overlap with those of other conditions such as depression, Gulf War Syndrome and fibromyalgia. A federal study now underway is designed to measure the activity of thousands of genes in 190 people, some with CFS, some without, to find a distinctive genetic fingerprint for chronic fatigue.

The goal, said Reeves, is a blood test for chronic fatigue.

''This illness is a nightmare that is extraordinary," said Dr. David Bell, a specialist in Lyndonville, N.Y.

''If you're lucky, you get over CFS in a couple of years. If you're not, it stays with you for the rest of your life."

Jean Harrison, 52, a former art restorer who lives in Salem, has been unlucky. She thinks she's had mild chronic fatigue since she was 6, but she wasn't diagnosed until she was 41, when her symptoms got worse. ''For a long time, my doctor thought I was depressed, so I exercised to help with that. But when the doctor realized I kept getting much worse after exercise, she concluded I had CFS. I was thrilled to finally get a diagnosis, after all those years of people saying, 'What's wrong with you?' "

Now, Harrison is ''almost housebound," she said. ''If I do too much, I can end up being asleep for days. If I haven't overextended, I can be awake for 7 to 8 hours. I can't exercise at all -- it's unthinkable to walk a mile. If I have supper with my family on a Sunday, I have to spend all day Monday in bed. It's a devastating illness."

Like Harrison, many people with chronic fatigue are first told they have depression. But the afflictions are quite different, with depression triggering an increase in the stress hormone cortisol and chronic fatigue a decline, said Harvard's Komaroff. While depression gets better with drugs like Prozac, the fatigue of CFS does not.

Jean Harrison's perplexing response to exercise is also typical of many chronic fatigue patients, perhaps because in them, exercise triggers the release of fatigue-inducing immune chemicals called cytokines. People with the syndrome sometimes can exercise as hard as healthy people -- they just feel awful for a day or two afterward, Reeves said.

''There is considerable evidence from published studies that in CFS the immune system is overactive," said Komaroff.

Given the complexity of Chronic Fatigue Syndrome, perhaps it's not surprising that treatments are piecemeal and not very effective and that some doctors get almost as discouraged as their patients.

''Very few doctors are willing to care for CFS patients because it is such a downer," said Dr. Hugh Calkins, director of electrophysiology at Johns Hopkins Medical Institutions in Baltimore.

Still, experts point to remedies that may help relieve some of the symptoms. In doses five to 10 times lower than those used for depression, tricyclic antidepressants like Elavil can improve sleep, said Komaroff.

And cognitive behavior therapy, which teaches people to re-evaluate their negative thoughts and behaviors, does help some people with CFS to use optimally the little energy they have.

But mostly, it's a game of patience -- and hope, that the strides in research ill translate into better diagnosis and ultimately, better treatments, for chronic fatigue.

http://www.boston.com/news/globe/health_ science/articles/2005/09/05/biology_of_chronic_fatigue_gains_focus?mode=PF