SEPTEMBER, 2006
CRACKING CHRONIC FATIGUE SYNDROME
A new Study by the CDC shows it’s not all in your head, but
in your genes.
By
Mary A. Fischer
The April morning she heard the report on NPR, Laura Hillenbrand began
her day as usual. Dragging herself out of bed, she took a shower and
then spent the next three hours recovering from it. While in the bathroom,
she mulled over the news: Scientists at the Centers for Disease Control
and Prevention (CDC) had found credible evidence of a biological cause
for chronic fatigue syndrome (CFS), the illness that Hillenbrand says
has caused her “suffering and incapacitation that is beyond my
ability to articulate.” Given that she is the author of the literary
phenomenon Seabiscuit: An American Legend, being stuck without the right
words would seem a rare occurrence.
The news from the CDC that day was significant—people with chronic
fatigue syndrome have a genetic quirk that causes them to over-respond
to physical and emotional stress. For the nearly one million Americans
estimated to suffer from the disease, the scientific validation meant
that the days of dismissing it as the head trip of whiny hypochondriacs
and the depressed were finally over.
Now, maybe, they can find a cure, Hillenbrand thought, as she stepped
out of the shower and fell into a chair. The simple exertion made her
dizzy and exhausted, and for the next few hours, she sat motionless,
trying to recoup her strength and calm her whirling vertigo.
Three to five times as many women as men have CFS, with symptoms that
include low-grade fever, nausea, memory loss, muscle pain, vertigo,
and the maddening combination of unexplained bone-weary tiredness and
sleeplessness. It can be as debilitating as multiple sclerosis and AIDS,
experts say, and often leaves its victims in bed, staring at the ceiling,
for weeks, even years. Many don’t recover, and those who do never
quite regain the sense of good health.
For Hillenbrand, even the seemingly easiest task becomes a Herculean
challenge. On most days she has only enough energy to leave the Washington,
D.C., house she shares with her fiancé for a two- or three-block
walk. Then it’s back home to rest. Sometimes she’s too weak
to sit up or even talk, and just reading the back of a cereal box makes
her dizzy. It took her four years to complete Seabiscuit, during which
she grabbed the moments she was able to concentrate and conducted all
her interviews over the telephone. Much of the time she was so sick
she worked from bed. In the past year, she has been out to dinner only
once, and even on a good day, she says, “I never feel anything
close to well.”
CFS struck her suddenly, triggered by a bout of food poisoning nearly
20 years ago, when she was a college sophomore. For others the onset
is more gradual. Michelle Akers, the world champion soccer star, chalked
up her daily flulike symptoms and utter exhaustion after college to
vigorous athletic workouts and an extensive travel schedule, and kept
pushing herself. In 1991, during the FIFA Women’s World Cup, she
scored ten goals, including five in one game, and was well on her way
to being named Player of the Century. But after a tour of public appearances,
she was barely able to drag herself to training and felt “like
a monster was sucking all the life out of me,” she recalls. Then,
during a 1993 competition in San Antonio, she collapsed on the field
and became delirious. “That was the beginning of understanding
what I was up against.”
Chronic Fatigue Syndrome was first recognized in the mid-1980s, with
outbreaks of the persistent flulike condition reported in Lake Tahoe,
Nevada, and Lyndonville, New York. Baffled physicians thought the culprit
might be a bacteria or viral agent carried in the air or water supply.
Later the strange illness was dubbed “the yuppie flu” and
mistaken for chronic Epstein-Barr virus syndrome, also called chronic
mononucleosis. (Researchers now believe the Epstein-Barr infection is
among the triggers for CFS.) Hillenbrand saw six doctors—they
told her she was a hypochondriac, mentally ill, going through puberty
(although she was 20 at the time)—before getting a correct diagnosis.
As recently as last fall, “roughly half the physicians who took
part in our focus groups said these people were fakers and lazy,”
notes Kim McCleary, president and CEO of CFIDS Association of America,
a patient advocacy and resource organization (the acronym stands for
chronic fatigue and immune dysfunction syndrome, another name for CFS).
Even today, despite the CDC findings, the American Medical Association
does not have an official position on whether CFS is an illness, although
the new research may spur them to take a further look. Those doctors
who do believe the disease is real—without knowing the cause—are
left to diagnose it by ruling out other illnesses. And because there’s
no treatment, they can only try to ameliorate the symptoms through a
variety of strategies like lifestyle changes, cognitive behavioral therapy,
and medications such as anti-depressants, painkillers, and stimulants.
For the groundbreaking CDC study, published in the April 2006 issue
of Pharmacogenomics, 227 volunteers—chronic fatigue patients and
healthy controls—checked into a Wichita, Kansas, hospital for
two days and underwent the most comprehensive testing of the illness
to date. “We worked these people up from head to toe,” says
the study’s coinvestigator, Suzanne Vernon, PhD, a molecular epidemiologist
and team leader of the CDC’s CFS Molecular Epidemiology Laboratory
Program. Psychiatric exams, sleep pattern evaluation, and analyses of
urine, hormones, and blood were all part of the testing—including
an assessment of the activity of some 20,000 genes.
“At first nothing jumped out at us,” says Vernon. So she
challenged four different teams—including experts in medicine,
molecular biology, bioengineering, chemical engineering, computer science,
and mathematics—to identify a biological indicator (in arthritis,
for example, the indicator is inflammation in the joints) that revealed
what was going wrong with people who had CFS. Working independently,
two teams delved into genetics and found that the DNA code in people
with CFS is different in genes that are important to both the immune
and sympathetic nervous systems—pointing, in particular, to three
genes related to the hypothalamic-pituitary-adrenal axis, which affects
the stress response. And compared with healthy subjects, all the CFS
volunteers had what’s called a high allostatic load, the cumulative
wear and tear on the body resulting from inadequate biological responses
to changes in the everyday environment as well as to emotional and physical
stressors—accidents, injury, the death of a loved one, toxic pollutants,
and illnesses. For people with the abnormal gene pattern, food poisoning,
which Hillenbrand got, and mono are among the triggers that might overwhelm
the immune system; in healthy people, those immune cells would adapt
to the trauma and start healing the body.
Michelle Akers believes that her CFS resulted in part from emotional
problems in her childhood. “Let’s just say I had some difficult
family challenges to work through” is how she puts it. Most CFS
researchers wouldn’t argue with her assessment. “Early life
adverse events—abuse, neglect, long-term malnutrition—can
really mess us up and change the architecture of the brain,” says
the CDC’s Vernon.
With the results of the CDC study, researchers predict that a diagnostic
test and treatment for CFS are only three to five years away. In the
meantime, new research will attempt to further our understanding of
the disease—for example, why so many more women get it than men.
“The CDC study also continues to legitimize an illness that the
mainstream medical community has been slow to take seriously,”
says McCleary. She and others agree that CFS is where multiple sclerosis
used to be 25 years ago, before MRI scans identified the disease’s
biological marker—lesions in the brain. With Epstein-Barr and
mono, more sophisticated blood tests can now definitively identify the
virus. “It has taken many illnesses years to earn credibility,”
says Anthony Komaroff, MD, professor of medicine at Harvard Medical
School and a longtime CFS researcher. “Multiple sclerosis used
to be seen as hysterical paralysis, and doctors used to tell patients
suffering from it, as well as those with lupus and rheumatoid arthritis,
that it was all in their heads. When a doctor can’t make a diagnosis
and give an effective treatment because medicine has not yet made the
necessary discoveries, the doctor can get frustrated.”
Akers, who retired from soccer in 2000 because of a lingering shoulder
injury and now has a 17-month-old son, suffered with her debilitating
symptoms for five years before finally seeing a doctor. “I’m
extremely stubborn, and I still played soccer. But I had to eliminate
everything else: no social life, and friends had to go grocery shopping
for me.” And although she went on for another ten years, winning
two World Cup championships and the gold medal in 1996, it was “at
a great cost,” she says. “The more I pushed, the more the
CFS left me with nothing.” Fortunately, today, except for hypotension
(low blood pressure) and migraines, her acute symptoms are gone. “I
will likely feel the effects of my career on my body for the rest of
my life,” she says, “but I don’t regret a second of
it.”
With the latest findings, Hillenbrand hopes for recovery. In the meantime,
she says, “I’m thrilled that people can’t dismiss
me as a nutcase anymore.” She’s using what precious energy
she has each day to write. In the afternoons, after resting much of
the morning, she works for maybe five hours on her much-anticipated
second book, a biography of the Olympic runner and World War II prisoner
Louis Zamperini, taking frequent breaks to still the spinning words
on the page. Although she’s largely housebound, her imagination
knows no such limits, as day after day she immerses herself in the explosively
energetic world of another champion.
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