Research: Research Symposia
Abnormalities in CFS deserve more comprehensive study
panel issues consensus statement on research issues
Research on the neuroendocrine system, which
the brain and glands that secrete hormones, could help explain many of the
symptoms of chronic fatigue syndrome (CFS). This was one conclusion reached by
a panel of experts that convened in March 2001 for the second in a series of
scientific symposia on CFS. The symposium was sponsored by The CFIDS Association of America and the U.S.
Centers for Disease Control and Prevention (CDC).
Several studies have suggested a
neuroendocrine component to CFS, but the exact role these abnormalities play is
still a mystery. For example, studies have found that some CFS patients have low
levels of cortisol, a hormone produced by the hypothalamic- pituitary-adrenal
(HPA) axis that plays a key role in sleep and fatigue, but more recent research
has not confirmed those findings.
"CFS is a multisystem disorder, and needs a
multidisciplinary approach," said Dimitris Papanicolaou, MD, assistant professor
of medicine, Emory University, and panel chair. "Researchers from diverse areas
of study need to collaborate to answer questions about neuroendocrine
involvement in CFS and drive treatment strategies to improve patients' daily
Following a day of presentations by experts
from around the world, an independent panel composed of researchers and
practitioners in the fields of biostatistics, endocrinology, epidemiology,
immunology, internal medicine, neurology, psychiatry and sleep disorders
developed a consensus statement on the key issues surrounding the role of the
neuroendocrine system in CFS.
The panel agreed that:
The nature of HPA function in CFS needs
to be clarified. There is evidence of HPA axis dysfunction in CFS patients,
but testing has yielded inconsistent results. This may be due in part to the
relapsing-remitting nature of the illness and to differences in research study
designs. The panel suggested that studies comparing CFS patients with and
without HPA axis dysfunction should be conducted.
Cytokine abnormalities, neuroendocrine
abnormalities, orthostatic intolerance and CFS may be interconnected.
Cytokines are chemical messengers that stimulate the HPA axis when the body is
under stress or experiencing an infection. A number of them, including tumor
necrosis factor alpha (TNF-a) and interleukin-6 (IL-6), have been implicated
in CFS. The panel noted these findings are intriguing in view of research
connecting CFS and a family of blood pressure-related disorders called
orthostatic intolerance (OI). There is evidence that excessive secretion of
inflammatory cytokines such as TNF-a may induce OI, although more studies
delineating the links between these abnormalities are needed.
CFS is not synonymous with depression.
The panel agreed that CFS should be differentiated from major depression.
Individuals with major depression have an activated HPA axis, but HPA axis
studies in CFS patients have been contradictory. Studies have shown that
corticotrophin releasing hormone (CRH) levels in the cerebrospinal fluid are
normal or even low in CFS patients, while they may be increased in depressed
individuals. Persons with CFS also demonstrate a diminished cortisol response
compared to persons with depression. The panel suggested that these data may
point toward a potential biological marker for persons with CFS compared to
persons with depression.
No link has been established between
CFS and stress. Past research has suggested that stressors such as viral
infections, traumatic life events, physical abuse and automobile accidents
may cause CFS symptoms. However, the panel agreed that there is not enough
evidence to date to establish a link between specific stressors and
neuroendocrine abnormalities in CFS and related disorders.
Sleep abnormalities may contribute to
CFS symptoms. Sleep disturbances have been shown to cause increased production
of IL-6 and TNF-a, and some researchers believe that they contribute
significantly to excessive daytime sleepiness in CFS. However, the panel
pointed out that studies of the association between HPA axis alteration,
cytokine secretion patterns, and sleep abnormalities have not yet been
conducted in CFS patients.
More research is needed to define the
neuroendocrine aspects of CFS. The panel outlined future research needs,
including studies to: evaluate stressors previously hypothesized to cause CFS;
test treatment strategies, including drugs to affect HPA axis activity; and
identify neuroendocrine activity in larger populations of persons with CFS,
including those that fit specific subtypes of the disease. Panelists also
suggested ways to overcome potential research barriers, such as conducting
long-term studies to capture the fluctuations in symptom severity most CFS
patients experience and developing human experimental models that temporarily
recreate the symptoms of CFS to identify potential biological markers for the
The CFS assessment symposia
series is designed to examine the role of the endocrine, circulatory and
immune systems in CFS. The symposia gather experts to evaluate research
findings, identify the most promising next steps for research, define research
and funding priorities, and create research collaboration teams.
The CFIDS Association of America,
which developed the symposia series, is the nation's leading organization working
to conquer this illness. Since 1987, the Association has invested over $12
million in education, public policy and research programs in its efforts to
bring an end to the suffering caused by CFS.
The CDC protects people's health and safety
by preventing and controlling diseases and injuries, enhances health decisions
by providing credible information on critical health issues, and promotes
healthy living through strong partnerships with local, national, and
international organizations. The agency conducts a CFS research program under
the auspices of the National Center for Infectious Diseases.
CFS, also called chronic fatigue and immune
dysfunction syndrome (CFIDS), is a debilitating and complex disorder
characterized by profound fatigue, pain, and cognitive problems that are not
improved by bed rest and may be worsened by physical or mental activity.