How Science Can Stigmatize: The Case of Chronic Fatigue Syndrome

Journal of Chronic Fatigue Syndrome, Vol. 14(4),2007

Leonard A. Jason, PhD
Judith A. Richman, PhD

Leonard A. Jason is affiliated with DePaul
University, Chicago, IL. Judith A.
Richman is affiliated with University of Illinois,
Chicago, IL.

Address correspondence to: Leonard A. Jason, Center
for Community Research, DePaul University, 990 W.
Fullerton Avenue, Chicago, IL 60614 (E-mail: xxxx).

The authors appreciate the funding provided by
NIAID (grant nos. AI 49720 and AI 055735).


KEYWORDS. stigma, epidemiology, myalgic
encephalomyelitis, myalgic encephalopathy



ABSTRACT.


Objective:

This article reviews issues involving the name of an
illness, chronic fatigue syndrome (CFS), along with
flawed epidemiologic approaches, which may have
further contributed to the diagnostic skepticism and
stigma that those with CFS encounter.

Methods:

Patient groups around the world are currently
engaged in a major effort to rename this syndrome
as either myalgic encephalomyelitis or myalgic
encephalopathy, to undo the negative effects of the
name previously given to this illness by scientists.
Moreover, during the last 15 years, estimated rates
of CFS have dramatically increased in both Great
Britain and the United States.

Results:

We suggest that the increases in both the United
States and Great Britain are due to a broadening of
the case definition to additionally include cases with
primary psychiatric conditions.

Conclusion:

Using a broad or narrow definition of CFS will have
crucial influences on CFS epidemiologic findings, on
rates of psychiatric comorbidity, and ultimately on
the likelihood of finding a biological marker and
identified etiology.


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INTRODUCTION

Chronic fatigue syndrome (CFS) is a highly
incapacitating illness, causing an estimated annual
loss of productivityworth $9.1 billion in the United
States (Reynolds, Vernon, Bouchery, & Reeves,
2004). Moreover, total direct and indirect costs due
to CFS range from $18.7 to $24 billion (Jason,
Benton, Valentine, Johnson, & Torres-Harding, 2007).

Patients with CFS are more functionally impaired
than those suffering from type 2 diabetes mellitus,
congestive heart failure, multiple sclerosis, and
end-stage renal disease (Anderson & Ferrans, 1997;
Buchwald, Pearlman, Umali, Schmaling, & Katon,
1996).

In a preliminary attempt to address CFS-related
mortality, Jason, Corradi, Gress, Williams, and
Torres-Harding (2006) analyzed a national CFS
foundation memorial list containing 166 individuals
with CFS who had died with this illness. Women were
approximately three times more likely to perish with
the illness than men.

Sixty percent of deaths were due to heart failure,
suicide, and cancer. Most importantly, the mean ages
of those dying from heart failure, cancer, and suicide
were 58.7, 47.8, and 39.3 years, respectively, and
these ages are considerably lower than of those
dying from heart failure (83.1), cancer (72.0), and
suicide (48.0) in the general population.



Despite its chronicity and severity, CFS remains
highly controversial. A particularly high percentage of
patients with this illness have experienced
disrespectful treatment by the health care system.
For example, Anderson and Ferrans (1997) found that
77% of individuals with CFS reported negative
experiences with health care providers.

Green, Romei, and Natelson (1999) found that 95%
of individuals seeking medical treatment for CFS
reported feelings of estrangement, and 70% believed
that others uniformly attributed their CFS symptoms
to psychological causes, despite findings that
comorbidity between CFS and psychiatric disorders is
considerably lower among patients with CFS (Taylor
& Jason, 2002).

Twemlow, Bradshaw, Coyne, and Lerma (1997) found
that 66% of individuals with CFS believed that they
were made worse by their doctors care.

Many health care professionals continue to doubt the
scientific validity of this diagnosis. We have argued
that the social construction of this disorder as a
psychogenic illness of neurotic women, similar to
earlier depictions of multiple sclerosis, have
contributed to the negative attitudes that health
care providers have toward thosewith this syndrome
(Richman&Jason, 2001; Richman, Jason,
Taylor,&Jahn, 2000).

Below, we review two issues: one political (involving
the name given to this illness) and the other
scientific (involving flawed epidemiologic
approaches) which may have further contributed to
the diagnostic skepticism and stigma that individuals
with this illness encounter.




How a Name Can Negatively Influence
Illness Attributions

The name selected to characterize an illness, such as
CFS, can influence how patients are perceived and
ultimately treated by medical personnel, family
members, and work associates. The term chronic
fatigue syndrome was coined by scientists in 1988
(Holmes et al., 1988).

The syndrome had previously been referred to by
various names, including myalgic encephalomyelitis.
In 1955, an outbreak of myalgic encephalomyelitis
occurred at the Royal Free Hospital in Great Britain,
described by Ramsay, the medical consultant in
charge (Hyde, Goldstein, & Lavine, 1992).

Later, Ramsay (1981) published a definition of this
disease under the name myalgic encephalomyelitis.
The most prominent of these criteria included:

(1) fatigue after minimal exertion (not daily fatigue)
and delay of recovery of muscle power after exertion
ends,

(2) one or more symptoms that indicate circulatory
impairment,

(3) one or more symptoms that indicate central
nervous system involvement (cerebral problems), and

(4) fluctuating symptoms.



Because fatigue was considered to be one of the
primary symptoms of this syndrome, in 1988, a group
of researchers, many of whom were at the Centers
for Disease Control and Prevention (CDC), coined the
name CFS and developed a newcase definition
(Holmes et al., 1988).

Patients believed that the term CFS trivialized the
seriousness of this illness, as the illness is typified
by many severe symptoms in addition to fatigue, and
fatigue is a common symptom experienced by many
otherwise healthy individuals in the general
population (Taylor, Friedberg, & Jason, 2001).

In addition, CFS is frequently confused with chronic
fatigue, which is a symptom of many illnesses,
including some psychiatric disorders.

The negative stigma associated with CFS may be
partially due to the trivializing name that has been
given to this disorder in 1988.

Two studies explored whether alternative names for
CFS (e.g., chronic fatigue syndrome, myalgic
encephalopathy) do influence attributions by medical
trainees (Jason, Taylor, Plioplys, Stepanek, & Shales,
2002) and college undergraduates (Jason, Taylor,
Stepanek, & Plioplys, 2001) regarding this syndrome.

Participants were randomly assigned to two groups,
with the difference between groups involving the
type of diagnostic label given for a case description
of a patient with prototypic symptoms of CFS.

Results showed that participants attributions about
CFS varied on the basis of the different diagnostic
labels used to characterize it.

**The myalgic encephalopathy label was associated
with the poorest prognosis, and this term was more
likely to be associated with a physiological rather
than a psychological cause to the illness. Many
patient groups believe that changing the name from
myalgic encephalomyelitis to CFS was a major
contributing factor to the stigmatization of this
illness, given the assumptions of a central
psychological rather than physiological etiology.



How Flawed Epidemiology Can Further
Contribute to Inappropriate Stereotypes

If medical personnel believe that CFS is a relatively
rare disorder and it is primarily caused by psychiatric
explanations, then physicians might minimize or
misinterpret the physical complaints of CFS patients,
and this could lead to the mistrust and lack of
communication that has been reported between
patients and medical personnel.

By the early-to-mid 1990s, the general consensus
was that CFS was a relatively rare disorder affecting
primarily white, middle-class women. Prevalence
estimates of this illness ranged from 2 to 7.3 (Gunn,
Connell,&Randall, 1993) or from 4.0 to 8.7 (Reyes et
al., 1997) persons per 100,000, suggesting that
there were less than 20,000 individuals in theUnited
Stateswith this illness.

But these estimates carried out by scientists at the
CDC used case ascertainment methods where
physicians identified patients who presented with
unexplained fatigue-related symptoms, and then
referred those patients for a medical examination to
determinewhether they met the criteria for CFS. Many
low-income individuals did not have access to
medical settings and thus might not have been
included in the prevalence studies. Moreover,
because many physicians doubted the existence of
CFS, they might not have made referrals to CFS
epidemiologic research studies (Richman, Flaherty, &
Rospenda, 1994).


In 1993, Jason et al. (1995) interviewed a random
community-based sample of approximately 1000
adults. Those individuals who self-reported having
CFS or many of the symptoms of CFS were examined
by a physician and interviewed by a psychiatrist to
determine whether they met case criteria for CFS.
The research teams diagnosis of 0.2% (200 per
100,000) wasmore than 10 times higher than the
rate originally reported by the CDC.

In a larger study conducted from 1995 to 1998, Jason
et al. (1999) screened a random sample of 18,675
individuals for CFS symptomatology. Approximately
0.42% of the sample was determined to have CFS,
with rates being higher among Latino and African
American respondents compared with White
respondents (Jason et al., 1999).

The results of this epidemiological study suggested
that this illness may affect approximately 800,000
people in the United States. Women, Latinos,
middle-aged individuals, and persons of
middle-to-lower socioeconomic status were found to
be at higher risk for this illness.

The findings directly contradicted the perception that
middle- to upper-class Caucasian women were at the
highest risk for this illness. Moreover, about 90% of
people identified as having CFS in this sample had
not been previously diagnosed by a physician before
participating in the study.

This finding highlights the limitations of prior CFS
epidemiological studies based solely on samples
recruited from hospitals or primary care providers.

These overall findings were later corroborated by
Reyes et al. (2003), in a CDC population based
prevalence study of fatiguerelated disorders. The
CDC used telephone calls to contact their sample of
33,997 households in Sedgewick County (Wichita),
Kansas (85.7% of their sample was White). The rate
of CFS was estimated to be 0.24%.




How Case Definitions Can Increase
Heterogeneity of Epidemiologic Estimates

These US-based studies indicated that, when using
appropriate community-based samples, the
estimated rate of CFS in the United States was
closer to 800,000 (0.42% or 420 cases per 100,000)
individuals instead of less than 20,000 (0.004%
0.0087% or 48.7 cases per 100,000).

In Great Britain, estimates of CFS were estimated to
be 2.6% or 2600 per 100,000 (Wessely, Chalder,
Hirsch, Wallace, & Wright, 1997).

While flawed epidemiologic methods can explain the
underestimate of CFS rates in the United States in
early 1990s, one needs to examine a broadened case
definition to understand why later rates in the United
States and Great Britain were so discrepant in the
direction of greatly increased prevalence estimates.


Wessely et al. (1997) indicated that of the 2.6%
with CFS, psychological disorders were absent in only
0.5%. Individuals diagnosed with CFS in this
epidemiologic study were subsequently compared
with a sample of people with CFS who had been
diagnosed from a hospital unit (Euba, Chalder,
Deale, & Wessely, 1996).

Of the community sample, 59% felt their illness
might be due to psychological or psychosocial causes
compared with 7% for the hospital sample. In the
community-based sample of Wessely, Chalder,
Hirsch, Wallace, and Wright (1996), 36 individuals
were diagnosed as having CFS.

Among this group, only 64% had sleep disturbances
and 63% had postexertional malaise.

These percentages are rather low, as both symptoms
are critical features of CFS. These findings might
provide a clue as to why Wessely and colleagues
found CFS prevalence rates that were appreciably
higher than those found by a second generation of
CFS epidemiologic studies in the United States.



It is of interest that the Great Britain CFS rates are
within the range of several mood disorders. Mood
disorders are the most prevalent psychiatric
disorders after anxiety disorders: for major
depressive episode, the 1-month prevalence is 2.2%,
and lifetime prevalence is 5.8% (Regier,Boyd, &
Burke, 1988).

Major depressive disorder is an example of a primary
psychiatric disorder that has some overlapping
symptoms with CFS.

Fatigue, sleep disturbances, and poor concentration
occur in both depression and CFS.

It is possible that some patients with major
depressive disorder also have chronic fatigue and
four minor symptoms that can occur with depression
(e.g., unrefreshing sleep, joint pain, muscle pain,
and impairment in concentration).

Fatigue and these four minor symptoms are also the
defining criteria for CFS. It is possible that some
patients with a primary affective disorder could be
misdiagnosed as having CFS.



While fatigue is the principal feature of CFS, it does
not assume equal prominence in depression
(Friedberg & Jason, 1998; Komaroff et al., 1996).

Several CFS symptoms, including prolonged fatigue
after physical exertion, night sweats, sore throats,
and swollen lymph nodes, are not commonly found in
depression.

Moreover, illness onset with CFS is often sudden,
occurring over a few hours or days, whereas primary
depression generally shows a more gradual onset.

Individuals with CFS can also be differentiated from
those with depression by recordings of skin
temperature levels and electrodermal activity
(Pazderka-Robinson, Morrison, & Flor-Henry, 2004).

CFS patients show more alpha electroencephalograph
activity during nonrapid-eye-movement sleep, but
this is not seen in dysthymic or major depressive
disorders (Whelton, Salit, & Moldofsky, 1992).

Bakheit, Behan, Dinan, Gray, and OKeane (1992)
found increased regulation of hypothalamic
5-hydroxytryptamine receptors in patients with
postviral fatigue syndrome but not in those with
primary depression.

Lutgendorf, Klimas, Antoni, Brickman, & Fletcher
(1995) found that CFS patients who experienced
greater cognitive difficulties had more abnormalities
in their immune system, with depression controlled
for, suggesting that the presence of cognitive
difficulties in CFS patients cannot be explained solely
by depressive or mood disturbances.

Some individuals with CFS might have had psychiatric
problems before and/or after CFS onset and yet,
other individuals may only have primary psychiatric
disorders with prominent How Science Can
Stigmatize The Case of CFs1 Including the latter
type of patients in the current CFS case definition
could confound the interpretation of epidemiologic
and treatment studies.



The CDC has recently released findings from another
community-based epidemiologic study that was
carried out in Georgia (Reeves et al., 2007).

Although the prior CFS prevalence ratewas estimated
to be 0.24 in Wichita, Kansas (Reyes et al., 2003),
the new CDC-estimated prevalence rates were
reported to be considerably higher with 2.54%
(remarkably similar to the 2.6% rate in Great Britain
(Wessely et al., 1997)).

The CDC now estimates that there are about 4
million people with this illness in theUnited States.

In this study, the authors screened for persons
who reported fatigue, problems with memory/
concentration, unrefreshing sleep or pain rather
than simply focusing on the single symptom of
fatigue, and the authors indicated that these
criteria increased the identified cases by 13%.

In addition, the authors used what they referred
to as standardized criteria to identify cases,2 and
this process identified three times the number of
CFS cases compared with the more usual
traditional way that the researchers have used
the Fukuda et al. (1994) criteria to identify cases.



As one part of the standardized CDC criteria, the
symptom inventory is used to operationalize the
symptoms of CFS (Wagner et al., 2005).

For each of eight critical symptoms, patients are
asked to rate the symptom on perceived frequency

(1 = a little of the time; 2 = some of the time;
3 = most of the time; and 4 = all of the time)

and severity or intensity of symptoms

(the ratings were transformed to the following scale:
1 = mild, 2.5 = moderate, and 4 = severe).

The frequency and severity scores were multiplied,
and the sums for the eight critical Fukuda et al.
(1994) symptoms were summed.

Even with summed scores for the empirical case
definition needing to be greater or equal to 25
(Reeves et al., 2005), the overall level of symptoms
seems relatively low for patients with classic CFS
symptoms (the criterion would be met if an individual
rated only two symptoms as occurring all the
timeone was of moderate, and the other of severe
severity).



In addition, the eight case definition symptoms were
based on a time period comprising the last month
compared with what is specified in the Fukuda et al.
(1994) criteria, which states: There needs to be the
concurrent occurrence of 4 or more of the following
symptoms, and all must be persistent or recurrent
during 6 or more months of the illness and not
predate the fatigue.

This expansion of the case definition has clearly led
to an expansion in the CFS prevalence estimate.



Additionally, forming the basis of this new CDC
empirical criteria are scores on the Medical Outcomes
Survey Short Form-36 (SF-36), assessing substantial
reductions in occupational, educational, social, or
recreational activities.

Using the SF-36, these criteria were defined as
scores lower than the 25th percentile on the physical
function, role physical function, social function, or
role emotional.

Because individuals need to meet only one of these
areas to meet the CFS criteria, individuals might not
have any reductions in key areas of physical
functioning, and only impairment in role emotional
areas (e.g., problems with work or other daily
activities as a result of emotional problems).

Ware, Snow, and Kosinsi (2000) found that mean for
role emotional for a clinical depression group was
38.9, indicating that almost all those with clinical
depression would meet the criteria for being within
the lower 25th percentile on this scale (which was a
score of =66.7).

In addition, King and Jason (2005) compared a group
diagnosed with CFS and a group diagnosed with
major depressive disorder, and the latter group had
lower scores than the group with CFS (37.8 vs. 48.9),
but both groups would have met the CDC criteria as
they both scored below >66.7.

In contrast, if the criterion has just been lower than
the 25th percentile on the physical function (>70),
participants with CFS would have met this criterion
as their average score was 44, whereas many within
the major depressive disorder group would have not
met this criterion, as their average score was 70.3.



The final instrument utilized as a component of the
new CDC empirical criteria is the multidimensional
fatigue inventory (MFI) (Smets, Garssen, Bonke, &
DeHaes, 1995).

Severe fatigue is defined as greater than or equal to
13 on the MFI general fatigue or greater than or
equal to 10 on the reduced activity.

However, general activity items refer to issues that a
person with depression might easily endorse. If a
person indicated that the following two items were
entirely true: I get little done, I think I do very little
in a day; they would meet criterion for this scale.

As for the criteria that Reeves et al. (2005) used, the
primary developer of the MFI had this to say:

Regarding the criteria suggested by Reeves, we have
no paper to back up their decision, but scanning their
paper it appears that they used the median of their
own data (E.M.A. Smets, personal communication,
June 29, 2006).

In a study of three groups with CFS, the mean How
Science Can Stigmatize The Case of CFs general
fatigue scores were 18.318.8 (Tiersky, Matheis,
DeLuca, Lange, & Natelson, 2003).

Our group is currently studying individuals with major
depressive disorder versus those with CFS, and we
are finding that individuals with a purely affective
disorder are being classified as having CFS with this
new empirical case definition (Najar, Porter, & Jason,
2007).




It is important to clarify the diagnostic criteria
underlying the two CDC community-based studies
(Reeves et al., 2007; Reyes et al., 2003), in so far
as their CFS-estimated prevalence rates have
changed so dramatically.

In the first CDC community-based epidemiology
study in Wichita, Kansas (Reyes et al., 2003),
Nisenbaum, Jones, Unger, Reyes, and Reeves (2003)
provided percentages of symptoms for 65 individuals
classified as having CFS.

Unusual fatigue post-exertion was found in 78.5%,
and difficulty thinking/concentrating or memory
problems was found in 76.9%.
As with the prevalence study of Wessely et al.
(1997), these classic CFS symptoms tend to be low,
suggesting an identified CFS group with fewer
symptoms.

In addition, 77% described their onset as gradual,
which contrasts with the sudden onset found in most
tertiary samples.

Of the individuals who were identified as having CFS
during the study that occurred over a 3-year period
(1997 through 2000), 58 were brought back for a
2-day inpatient study that occurred from December
2002 to July 2003, and only 16 (28% of the original
group diagnosed with CFS) had a current consistent
diagnosis of CFS, using traditional methods of
making this diagnosis.

A review of prospective outcome tertiary care studies
in CFS patients (Cairns&Hotopf, 2005; Joyce, Hotopf,
& Wessely, 1997) reveals that substantial recovery
occurs in less than 10% of cases. It appears that
patients recruited from community-based samples
might be very different from those from tertiary
samples, at least in terms of classic symptoms and
maintenance of CFS status over time.


In addition, 6 of the 16 (38%) of the current CFS
cases had been previously diagnosed with major
depressive disorder with melancholic features during
the period from 1997 through 2000 (Reeves et al.,
2005).

These scientists from the CDC as well as others
(Reeves et al., 2003) had previously recommended
that these individuals should be excluded from the
CFS case definition.3

When these investigators employed an empirically
derived system2 (that was used in deriving the
higher prevalence rates of 2.54% in the Georgia
community-based study), 43 rather than 16
individuals who had been traditionally diagnosed as
having CFS met this new system.

Clearly, this newly developed empirical system
diagnoses additional people with CFS. It is very
possible that this new empirical classification does
identify a group of individuals with high levels of
fatigue, impairment, and symptoms, but it might
also be identifying a group with high chronic distress
and illness, rather than CFS as a unique disorder.



Patient groups around the world are currently
engaged in a major effort to rename this syndrome
as either myalgic encephalomyelitis or myalgic
encephalopathy, to undo the negative effects of the
name previously given by scientists.

This is a daunting task, and few scientists have been
willing to substitute using this older term in their
writings. These efforts are patient inspired and they
represent a political struggle between the scientific
community, which continues to prefer the term CFS,
and the patient community, which almost
unanimously wants the name changed, in an effort to
alleviate some of the stigma and speculation about
the authenticity of their illness.

There are several scientists that have joined efforts
to use both terms with two new case definitions, one
for adult cases (Carruthers et al., 2003) and the
other for pediatric cases (Jason, Bell et al., 2006),
which referred to the illness as ME/CFS (myalgic
encephalomyelitis/chronic fatigue syndrome).



During the last 15 years, estimated rates of CFS
have dramatically increased in the United States. For
example, the CDC initially estimated that 48.7
individuals per 100,000 (Reyes et al., 1997) had CFS,
and later using community-based methods increased
estimates to 240 cases per 100,000 (Reyes et al.,
2003).

More recently, the estimated rates have increased to
2540 cases per 100,000 (Reeves, 2007). It is at least
possible that the increases in the United States are
due to a broadening of the case definition and
possible inclusion of cases with primary psychiatric
conditions.

Some CFS investigators would not see this as a
confounding problem because they believe that high
rates of psychiatric comorbidity indicate that CFS is
mainly a psychiatric disorder (Abbey, 1993).

CFS and depression are two distinct disorders,
however, even if they share a number of common
symptoms. Most importantly, the erroneous inclusion
of people with primary psychiatric conditions in CFS
samples will have detrimental consequences for the
interpretation of epidemiologic, etiologic, and
treatment efficacy findings.



Reeves et al. (2005) claim that the empirical
definition identifies people with CFS in a more
precise manner than can occur in the more traditional
way. It is primarily the use of this new empirical
case definition that has led to the increase in CFS
prevalence rates in the United States. In their use of
the empirical case definition, several changes
occurred to what had been previously been
recommended by an international expert committee
(Reeves et al., 2003) of recommendations for the
case definition of Fukuda et al. (1994).

First, rather than excluding those with depressive
disorder with melancholic features, only those with a
current condition were excluded as opposed to what
had been recommended.3

Of interest, of those 16 within the Reyes et al.
(2003) study who had been classified with CFS using
the more traditional methods, 6 had a past history of
major depressive disorder with melancholic features
(Reeves et al., 2005); and it is unclear how many of
those 43 who were diagnosed using the empiric case
definition had past depressive disorder with
melancholic features.

These individuals should have been excluded, and by
including them, the broadening of the case definition
has the potential to bring into the CFS category
those with a primary psychiatric condition.


More importantly, there was little agreement
between the empirical method of classifying
individuals and the more traditional method of
comparing whether an individual met the case
definition on their critical symptoms.

Rather than assuming that this might be a
problem with the empirical case definition, they
concluded that the more traditional way of
diagnosing patients was flawed. As an example of
this problem, one individual who was classified as
being in remission for CFS using the traditional
method was diagnosed with current CFS using the
CDCs empirical approach.



Papers are now appearing in the literature using this
empirical case definition of CFS, and many have
received considerable media attention.

Rajeevan et al. (2006) found that the glucocorticoid
receptor gene (NR3C1) was a potential mediator of
CFS, and yet no association was found between two
classic disability measures the SF-36 physical
function and role function and the genetic markers.


Also of interest, a series of articles were recently
published on the Wichita study in Pharmacogenomics
(Vernon & Reeves, 2006), using the CFS empirical
case criteria. Below several of the articles within this
special issue are examined.

Gurbaxani, Jones, Goertzel, and Maloney (2006)
found that the depression score was the most
effective variable discriminating between CFS cases
and controls, whereas 20 biological variables only
achieved classification accuracy slightly better than
chance.

Craddock et al. (2006) found that the Zung
self-rating depression scale had the highest
correlation with the empirical illness classification
(CFS, unexplained fatigue but symptoms or severity
short of the CFS case definition, and nonfatigued).

Vollmer-Conna, Aslakson, and White (2006) used the
latent class analysis to define a six-class
interpretable solution in women. However, the
sample included those with melancholic depression,
because as the authors note, the decision to exclude
them from the CFS case definition was not based on
empirical data.

In addition, the mean body mass index for five of the
six classes indicted that the participants were
overweight, and obesity probably played a prominent
role in the illness in at least two of the groups (over
half of the CFS cases empirically defined were in
these two groups).

Aslakson, Vollmer-Conna, and White (2006) indicated
that classes 5 and 6 had the highest percentage of
empirically derived CFS cases (73% and 64%), these
two classes had the highest proportion of comorbid
major depressive disorders (36% and 27%), and
these classes had the highest mean Zung depression
scores (Aslakson, Vollmer-Conna, & White, 2006;
Fostel, Boneva, & Lloyd, 2006).

In addition, one individual who was empirically
classified as having CFS was in the class designated
as being well.

Fostel, Boneva, and Lloyd categorized patients with
CFS into those with and without past major
depressive disorder with melancholic features, and
the coefficient of a fatigue factor was over twice as
high for the CFS group without major depressive
disorder with melancholic features.


Other researchers have found that the severity of
fatigue differentiates those with CFS and those with
major depressive disorder (King & Jason, 2005).

This finding also supports the possibility that the
CDC sample includes those with CFS and those with
primarily a major depressive disorder.

Other groups that have analyzed the CDC Wichita
data set have found that single-nucleotide
polymorphism data are not useful in identifying CFS
patients (Glynn, Emmert-Streib, & Mushegian, 2006)
and that there are no biological markers that consist
of a small number of genes that can be useful as
independent classifiers of CFS (Kennedy et al.,
2006).

Others have also been critical of these studies of
gene expression for not confirming microassay
analyses with real-time polymerase chain reaction
(Kerr et al., 2006).


Heim et al. (2006) recently used this new empirical
case definition and the Wichita study to explore the
influence of early adverse experiences on risk for
developing CFS.

The authors concluded that childhood trauma is an
important risk factor for CFS. In fact, among those
with CFS, 62.8% had some type of early abuse.

By contrast, Taylor and Jason (2002) found
prevalence rates of sexual and physical abuse history
among individuals with CFS to be comparable with
those found in individuals with other conditions
involving chronic fatigue, including medically based
conditions. Relative to those with CFS who report
such history, most individuals with CFS do not report
histories of interpersonal abuse.


Other researchers, such as Kato, Sullivan, Evengard,
and Pedersen (2006) have used the term chronic
fatigue-like illness to characterize cases derived from
a telephone interview, but lacking a medical
examination or psychiatric screen.

This research group concluded that higher emotional
instability and self-reported stress in the premorbid
period were predictive of a more than 50% greater
risk of developing chronic-fatigue like illness a
quarter of a century later.

However, the key issue is whether this study is
capturing chronic fatigue that is caused by
psychiatric factors or actual CFS cases.



Cantwell (Cantwell, 1996) argues that diagnostic
criteria should specify which diagnostic instrument to
use, what type of informants to interview, and how
to determine presence and severity of the criteria. It
is necessary to specify a certain number and type of
symptoms that should be present to make a
particular diagnosis.

In addition, to determine the importance of the
number and type of symptoms, definitions of fatigue
should also include specific guidelines pertaining to
the importance of symptom severity in the diagnostic
procedure.

The Reeves et al. (2005) article clearly used
instruments (such as the SF-36) to make diagnostic
decisions rather than additionally utilizing more
specific criteria involving critical diagnostic aspects
of the illness (for example, whether with rest, all
symptoms disappear).

Given the high variability in symptom severity among
persons with fatigue, standardized procedures should
be employed for determining whether or not a
particular symptom is severe enough to qualify as
one of the symptoms required for the diagnosis of
fatigue.

But one needs to be extremely careful about deciding
when standardized instruments and scores need to
additionally include contextual issues, and often they
do not.

For example, if a patient endorses a symptom such
as postexertional malaise, standardized questions
should include duration, frequency, and severity of
the symptom including onset, pattern, intensity, and
associated factors (see Hawk, Jason, &
Torres-Harding, 2007).

Clinical judgment, which has been used in most past
studies to diagnoses CFS, remains an important role
even for diseases like lupus, which use a
combination of clinical judgment, patient report, and
objective measures to come up with a diagnosis.

This currently is not occurring with the CFS
empirical case definition developed by the CDC.


Some researchers have posited that fibromyalgia
syndrome (FMS), CFS, and irritable bowel syndrome
(IBS) can be considered functional somatic
syndromes (Barsky & Borus, 1999).

Functional somatic syndromes are characterized by
diffuse, poorly defined symptoms that cause
significant subjective distress and disability, cannot
be corroborated by consistent documentation of
organic pathology, and are highly prevalent even in
healthy, nonpatient groups (Barsky & Borus, 1999).

Accurate measurement and classification of CFS,
FMS, and IBS is imperative when evaluating the
diagnostic validity of controversial disease entities
alternatively labeled, functional somatic syndromes.

For example, results of a study by Taylor, Jason, and
Schoeny (2001) provided support for distinctions
between the five conditions of FMS, CFS, somatic
depression, somatic anxiety, and IBS, but this will
occur only when using symptom criteria that match
actual diagnostic criteria for these illnesses.

Measurement that fails to capture the unique
characteristics of these illnesses might
inaccurately conclude that only distress and
unwellness characterize these illnesses, thus
inappropriately supporting a unitary hypothetical
construct called functional somatic syndromes.

Ultimately, using a broad or narrow definition of
CFS will have important influences on CFS
epidemiologic findings, on rates of psychiatric
comorbidity, and ultimately on the likelihood of
finding biological markers.




````


NOTES

1.  Wessely and associates administered a simple
biochemical screening and gathered medical records
on participants, but they did not evaluate their
patients in a comprehensive, controlled manner.

Moreover, these researchers employed the Revised
Clinical Interview Schedule (CIS-R), an instrument
that was not designed to detect specific exclusionary
psychiatric conditions as defined by the current CFS
criteria (e.g., melancholic depression, drug
abuse/dependence, alcohol abuse/dependence,
anorexia nervosa, bulimia nervosa, and psychotic
disorders).


2.  Reeves et al. (2005) have advocated using
empirical methods to classify CFS, using the Medical
Outcomes Survey Short Form-36 (SF-36), the
Multidimensional Fatigue Inventory (MFI) and the
CDC Symptom Inventory (Wagner et al. 2005).

Substantial reductions in occupational, educational,
social or recreational activities were defined as
scores lower that the 25th percentile on the physical
function (>70), or role physical function (>50), or
social function (>75), or role emotional (>66.7)
subscales of the SF-36.

Severe fatigue was defined as greater than or equal
to 13 on the MFI general fatigue or greater than or
equal to 10 on the reduced activity. Individuals also
needed to have four or more symptoms and scoring
greater than or equal to 25 on the Symptom
Inventory Case definition (a sum of the products of
the frequency and intensity scores of the 8 CFS case
definition symptoms).



3.  If their major depressive disorder with
melancholic features had been resolved for more
than 5 years before the onset of the current
chronically fatiguing illness, Reeves et al. (2003)
recommend that the person could be diagnosed with
CFS.

But in this sample (Reeves et al. 2005), as all
individuals had been diagnosed with CFS at one time
in the past, their depressive disorder with
melancholic features could not have resolved itself 5
years before the onset of their CFS illness.



````

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Submitted: July 10, 2007 Revised: January 8, 2007
Accepted: January 20, 2007