Research holds the key to conquering
chronic fatigue and immune dysfunction syndrome (CFIDS). Experts are testing a
vast number of theories about what causes CFIDS, from viral agents to hormone
imbalances to neurological irregularities. At the same time, they're looking at
drugs and other treatments that could ease symptoms or even reverse the course
The Chronicle will devote 2002 to exploring the state of
some of these research efforts. This is the first in a periodic series of
question-and-answer sessions with leading CFIDS researchers.
Is CFIDS a disease of genetics or environment? Researchers
at the University of Washington are trying to answer this key question by
studying an unusual group of human subjects: twins.
Syndrome Cooperative Research Center is testing hundreds of twin pairs to learn
how genes may influence the development of CFIDS. The Chronicle asked center
researcher and Associate Director Niloofar Afari, PhD, to explain what's been
discovered so far - and what may lie ahead.
Twins are very
important because of who they are. Monozygotic, or identical, twins share all of
their genetic materials. Dizygotic twins, also known as fraternal or
non-identical twins, share on average about half of their genetic material. This
is important because it helps distinguish between the genetic and the
environmental causes of illnesses.
Say you study
two people with the
same genetic material. If one of them has a disease or shows certain test
results and the other one does not, you can figure that there may be
environmental factors at play. We're trying to apply those research strategies
to chronic fatigue syndrome (CFS), to look for possible biological and
do you conduct your
We have several
things going on. We started established in 1996. It's a volunteer registry. We
have put out the word to twins organizations, CFS organizations and physicians
who treat people with CFS or fibromyalgia (FM). We're interested in twins where
either one or both have chronic fatigue, CFS or FM.
Right now the
registry is probably
close to 250 pairs. We have the whole gamut of twins, monozygotic and dizygotic,
including some opposite-sex pairs. Some are discordant, meaning that one twin
has chronic fatigue, CFS or FM and one twin doesn't. Others are concordant,
meaning they both have one of these conditions.
a huge number of
measures on participants in this registry. The booklet of questionnaires that we
send out to them is about an inch thick. It has a medical history to fill out,
including symptoms of fatigue and other problems. The twins keep a sleep
diary, which lasts for two weeks, where they record information about their
sleep patterns. There's a whole battery of other measures about stress,
coping, family disease history and social support, general levels of pain and
fatigue, personality, social support, any kind of threatening life experiences
they've had -- you name it, we ask it.
We also use the
registry to pinpoint
a group of monozygotic, discordant twins to do more comprehensive evaluations.
That's what we call the intensive study. We are in the second round of these
intensive studies. For the first intensive study, we brought in 21 pairs of
discordant monozygotic twins from all over the country to Seattle. We did a
week-long battery of tests. Again, you name it, we did it. Everything from
psychiatric interview to a three-night sleep study, exercise testing, blood
draws, hormonal levels. We tried to cover tests that would relate to all the
theories about the causes of CFS.
For the second
round, we're bringing
in as many of those twin pairs as possible and doing follow-up testing. The
tests are along slightly different lines, because we're looking for slightly
different things. But again, we're doing exercise testing, sleep studies, brain
imaging, psychiatric evaluations. This will help us get some longitudinal
information, to see how things may change over time.
have you learned from
looking at the discordant pairs, we have some interesting but unanticipated
findings. For example, there don't appear to be huge differences in
how the twins cope with things in their lives. There are some differences, like
the use of a few particular coping strategies, but certainly not as big as we
might have expected.
about the first
Again we have
some interesting but unanticipated findings. Mainly, we have found that
with our sample of discordant identical twins, both members of the pair show
similar abnormal findings on a number of tests. For example, in exercise
testing, they both appear to be doing similarly -- but similarly poorly. So even
though we are not finding huge differences between the CFS and non-CFS twins, we
have some intriguing results that we are now exploring in more
You can learn a lot from the test results. If they do show a
difference, you can attribute that to what's different about the twins, which is
their environment. If they don't show a difference, you can attribute that to
what's the same - their genetics.
Basically, when we've not been able to
show too many differences -- such as with the poor exercise results - that means
that there's quite possibly a hereditary component to chronic
you definitely say
there's a genetic component to CFS?
No, I don't think
we're there yet. At this point, I would say that things are pointing in the
direction of genetics, but I couldn't say right now that there's some genetic
cause. We're pretty early on in this line of research.
Also, as is the
case with many other illnesses, CFS is likely the result of both genetics
and the environment. That's what we call the gene by environment
are you looking for
In the previous
round, we found evidence that the twins are not so different from each other,
but yet abnormal in many of their findings. In this round, we are looking more
closely using ever more precise assessments to identify the underlying
mechanisms for CFS. That is, we're looking for why one of them would
exhibit symptoms while one won't. For example, one of the things we're focusing
on is perception. The question is how the twin with CFS perceives things
differently than the person without CFS.
be seen as something
that is biologically or genetically driven. Two people could have exactly the
same experience, yet the body systems of one would sense it, perceive it,
differently than those of the other person. This is important: By studying
perception, we don't mean that it's all in your head. It doesn't mean that you
think you have CFS and therefore you do. It means that the bodies of people with
CFS may sense things differently. These differences could become diagnostic
markers for CFS.
For example: One of the studies we're doing is pain
testing. We're trying to establish the twins' pain thresholds. At what point do
they experience pain, and at what point do they perceive the pain to be
There's no doubt that people feel pain. You give them a
strong enough stimulus, they're going to say "ouch." But at what point does
somebody say "ouch"? That's perception. We want to know at what point the
systems of a CFS twin says "ouch," and whether that's different than with the
non-CFS twin. That could be a diagnostic marker for CFS.
It's the same
with fatigue. We would test this by putting someone on an exercise bike. You ask
them to keep going to see at what point their bodies say, "I'm pretty tired,"
and what point they say, "I'm so exhausted I can't go on any more."
don't know what we're going to find. But once we gather the data, we'll start
looking at how to apply it. We're supposed to be finished with this by 2004.
Then we'll get ready for the next round of studies.
The research center is interested in enrolling
more twin pairs for its registry. One or both of the twins must have CFS or FM.
Contact Megan Belcourt at 206-521-1935, or call toll free at 1-888-223-0868 and
ask for Megan.