Etiology 371prevalence estimates and the related issue of psychiatric co-
morbidity.
Lawrie and Pelosi (1995) found a prevalence rate of 560
per 100,000 among a sample of 1,000 patients. The respon-
dents were resurveyed one year later, and a random sample
were interviewed again 18 to 22 months later (Lawrie,
Manders, Geddes, & Pelosi, 1997). After controlling for con-
founding variables, only premorbid fatigue score was a sig-
ni“cant predictor for developing chronic fatigue. (Emotional
morbidity and physical attribution for fatigue were not risk
factors.) Of the new chronic fatigue cases, 75% of those who
had consulted a general practitioner for fatigue were proba-
ble psychiatric cases, whereas only 17% of those who had
not consulted a general practitioner were psychiatric cases.
Two cases of CFS were identi“ed among the new chronic
fatigue cases, and two cases of patients who had been ill at
the time of the “rst prevalence study were found. (The cases
were equally divided between the sexes.) The two incident
cases described having recovered within a year (only one
had a psychiatric diagnosis), whereas the two more long-
standing prevalent cases had psychiatric diagnoses and nei-
ther had recovered 18 months later. At that follow-up,
Lawrie et al. (1997) estimated the annual incidence of CFS
to be 370 per 100,000 and the prevalence to be 740 per
100,000.
From 1995 until 1998, Jason, Richman, and colleagues
(1999) attempted to contact a strati“ed sample of 28,673
households in Chicago by telephone. Of that sample, 18,675
individuals were screened for CFS symptomatology. The
sample was strati“ed to ensure a representative sample of
the diverse ethnic and socioeconomic groups comprising the
Chicago general population. Based on the initial screening,
participants with signi“cant fatigue and CFS symptoms were
selected to receive a psychological evaluation and medical
examination. Approximately .4% of the sample was deter-
mined to have CFS, and rates of CFS were higher among
Latino and African American respondents when compared to
White respondents (Jason, Richman, et al., 1999). These data
suggested that there might be as many as 800,000 adults in
the United States with this syndrome, suggesting that it is
one of the more common chronic health conditions. Data
were also collected for youth, and the “ndings indicated a
CFS prevalence of .06%, or 60 cases per 100,000 (Jordan
et al., 2001).
Finally, Reyes, Nisenbaum, Stewart, and Reeves (1998)
reported on the “rst phase of a CDC population-based preva-
lence study of fatigue-related disorders. The CDC used tele-
phone calls to contact their sample of 34,018 households in
Sedgewick County (Wichita), Kansas (87.8% of their sample
was White). The rate of CFS was estimated at about 240 per
100,000. The CDC has now recommended that all future epi-
demiologic research involve randomly selected, community-
based samples.ETIOLOGYPeople with CFS appear to have two basic problems with
immune function: immune activitation as demonstrated by
elevations of activated T lymphocytes, including cytotoxic
T cells and elevations of circulating cytokines; and poor
cellular function, with low natural killer cell cytotoxicity
and frequent immunoglobulin de“ciencies (most often
IgG1 and IgG3) (Evengard, Schacterle, & Komaroff, 1999;
Patarca, Fletcher, & Klimas, 1993; Patarca-Montero, Mark,
Fletcher, & Klimas, 2000). Landay, Jessop, Lennette, and
Levy (1991) were the “rst group of researchers to “nd that
the CD8 CD11b suppressor cell population was reduced in
patients with CFS, while the activation markers (CD38 and
HLA-DR) had increased. This suggests that decreased sup-
pressor cells lead to a hyperimmune response.
A variety of physical and psychological stressors can
cause corticotropin-releasing hormone (CRH) to be released
from the paraventricular nucleus of the hypothalamus. CRH
causes adrenocorticotropin (ACTH) to be released from the
anterior pituitary, and ACTH in turn stimulates cortisol re-
lease from the adrenal cortex. A frequently cited biological
study by Demitrack et al. (1993) found low levels of cortisol
in CFS patients, which might be due to a de“cit in CRH.
De“cits in cortisol have been linked to lethar gy and fatigue,
and this de“cit might be contributing to the overactive im-
mune system. In a summary of the literature, Scott and Dinan
(1999) mentioned that patients with CFS have a reduced
adrenal secretory reserve and their adrenal gland size is
smaller compared to healthy subjects, whereas in major
depression, enlarged adrenal glands are found. Neurotrans-
mitters, including serotonin (5HT), are also involved in the
release of CRH. Serotonin, according to Scott and Dinan,
might play a role in the genesis of CFS, as altered 5HT neu-
rotransmission seen in patients with CFS may account for
disturbed sleep, muscle pain, gastrointestinal problems, and
mood alterations. Scott and Dinan mention that vasopressin
(VP) also acts in a synergistic fashion with CRH in stimulat-
ing ACTH release, and low VP levels have been found in
subjects with postviral fatigue syndrome. Wessely (1993),
however, states that it is simplistic to view CFS as a de“-
ciency in CRH, but some abnormality in CRH metabolism
possibly underlies both depression and CFS.
Another important biologically based explanation involves
the 2 -5 A antiviral pathway, which causes the production of