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The latest information
on research, treatment and diagnosis of CFIDS and related
scientists have found an aberration in some CFS patientsí serotonin gene and
hypothesize that it may be related to the pathophysiology of
the condition. Serotonin is a brain chemical that regulates sleep, appetite,
pain, mood, emotion and inflammation.
Serotonin gene abnormality in CFS
CFS patients were more likely to have rare forms of the
serotonin transporter gene compared to controls. The so-called longer gene
variants were seen in 40 of 156 genes from CFS patients, and only 12 of 100
genes from controls. This genetic alteration may result in a person having lower
levels of active serotonin and may also increase susceptibility to CFS,
according to the researchers. Serotonin interfaces with the
hypothalamic-pituitary-adrenal (HPA) axis and may play a role in the
endocrine abnormalities that have been found in CFS. The study
was published in Biochemical and Biophysical Research Communication in
Serotonin inhibitor may alleviate CFS
out of five patients treated with granisetron, a serotonin
agonist, saw marked improvements in fatigue and treated with
granisetron, a serotonin agonist, saw marked improvements in fatigue and
function within two weeks of starting therapy, according to an article in the
September 2003 issue of Netherlands Journal of Medicine. The positive
results faded two weeks after discontinuing treatment.
The promising results have led to the initiation of a
placebo-controlled, blinded study. Although the present study was open-label and
a placebo effect canít be ruled out, there is a strong rationale behind the
study. Increasing evidence points to an upregulation of serotonin in the
pathogenesis of CFS, which would explain why serotonin agonists might be
effective, and why antidepressants in the selective serotonin reuptake inhibitor
(SSRI) category, such as Prozac, have not worked as well.
Editorís note: Contradictory research findings, such as
appear in the above two studies, may reflect variable study methodologies, such
as different patient selection criteria or ways of interpreting findings. The
only way to clear up these and other mysteries of CFIDS is through research
studies which involve large numbers of patients and use proven study
methodologies and techniques.
Milnacipran treats FM pain
Results of a
Phase II study showed that milnacipran is effec tive in treating fibromyalgia
pain and that its impact on pain is distinct from its antidepressant properties.
The drug worked equally well in depressed and nondepressed FM patients, but the
placebo response was stronger in depressed patients. This "suggests that the
pain experienced by these patients is not directly related to their mood,"
according to Jay D. Kranzler, MD, PhD, of Cypress Bioscience, the sponsor of the
Milnacipran is a new class of drug that acts on two key
neurotransmitters, norepinephrine and serotonin. It is available in 22
countries, but not yet in the U.S. Cypress Bioscience launched a Phase III
clinical trial of the drug as an FM treatment in October.
CFS research, diagnosis clarified
international group of CFS researchers offers long-needed clarification of the
1994 CFS case definition in the December 31 issue of BMC Health Services
Research. The authors make a particular effort to explain "exclusionary
conditions," which is a key part of the 1994 case definition, but has been
difficult to interpret and apply.
Exclusionary conditions are medical or psychiatric conditions
that could plausibly cause CFS symptoms, such as multiple sclerosis or
chemo-therapy treatment. Because the biology of CFS is not understood,
researchers must screen potential subjects for exclusionary conditions to rule
out the possibility that their findings could be attributed to another condition
(or set of conditions) present in the subjects.
Although the 1994
definition was written only
for research settings, it was adopted by physicians to
diagnose their patients because no alternative clinical
guidelines existed. The new paperís authors acknowledge that the concept of
exclusionary conditions may have less importance in clinical practice. They
state, "In the clinical setting, patients with exclusionary conditions may be
diagnosed and manage as having CFS on the basis of the physicianís medical
opinion as to whether the exclusionary condition is likely to be a major
contributor to the patientís fatigue." While this change seems to broaden the
definition of CFS, it likely reflects how the illness is actually diagnosed by
The paper clarifies other ambiguities in the original case
definition. For example, the case definition concept that "rest should not
substantially alleviate fatigue" has sometimes been misinterpreted to suggest
that if you feel better after resting, you do not have CFS. The authors explain
that this statement was intended to distinguish CFS from the "fatigue associated
with overwork that resolves when the excessive demands end."
The article also makes a concerted effort to standardize
research instruments by recommending specific instruments to measure particular
symptoms. One major problem in CFS research has been the use of vastly
differ-ent tests to assess the same symptom (such as cognitive impairment),
making it nearly impossible to compare one studyís results to anotherís. If
adopted by researchers, these recommendations should greatly improve
comparability of research.
The full text of this article is available at
Progesterone elevated in women with CFS
In a small Canadian study, women with CFS had significantly
higher levels of progesterone and its metabolite
isopregnanolone compared to healthy controls. These differences could not be
attributed to medications or depression ó further evidence, say the researchers,
that CFS differs from depression.
The authors, writing in the February 2004 issue of
Psychoneurendocrinology, suggest this progesterone elevation may explain the
common finding that cortisol, another hormone, is low in CFS. Progesterone
influences cortisol production, but cortisol can be inhibited if progesterone
metabolism is diverted toward the production of the ring-A metabolites,
particularly isopregnanolone, which was significantly elevated in the CFS
CFIDS Glossary: Terms You Need to
Agonist: A drug or chemical that
combines with a cell receptor to produce a physiologic reaction typical of a
naturally occurring substance. A serotonin agonist is able to mimic the effects
of serotonin by stimulating activity at the brainís serotonin receptors.
Endocrine: Glands (or the system of
glands) that secrete hormones directly into the circulatory system. Hormones
regulate many organs in the body, and because they have such widespread effects,
many of the leading theories about CFS involve abnormalities in the endocrine
Metabolite: A substance produced by
metabolism or by a metabolic process. Metabolism is the sum of the physical and
chemical processes in the body and the process which makes energy available to
Pathophysiology: The functional
changes associated with or resulting from disease or injury, as opposed to
structural defects. The pathology of CFS would set the disease in motion, while
the pathophysiology would explain the effects of the disease in the body.
Sources: Dictionary.com and Pharma-Lexicon.com