Symptom Occurrence in Persons with Chronic Fatigue Syndrome

L.A. Jason, S.R. Torres-Harding, A.W. Carrico and R.R. Taylor

DePaul University, Center for Community Research, 990 West Fullerton Road,

Chicago, IL 60614, USA. Corresponding author. Tel.: +1-773-325-2018; fax: +1-773-325-4923. email: Ljason@depaul.edu

Abstract

This investigation compared differences in the occurrence of symptoms in

participants with CFS, melancholic depression, and no fatigue (controls). The

following Fukuda et al. [Ann. Intern. Med. 121 (1994) 953] criteria symptoms

differentiated the CFS group from controls, but did not differentiate the

melancholic depression group from controls: headaches, lymph node pain, sore

throat, joint pain, and muscle pain. In addition, participants with CFS

uniquely differed from controls in the occurrence of muscle weakness at

multiple sites as well as in the occurrence of various cardiopulmonary,

neurological, and other symptoms not currently included in the current case

definition. Implications of these findings are discussed.

1. Introduction

Chronic fatigue syndrome (CFS) remains a poorly understood and controversial

disease, because the exact causal agents are unknown, physical signs and

symptoms are variant, and diagnostic laboratory tests have poor sensitivity

and specificity (Holmes and Jason). In the absence of laboratory tests or

other objective indicators, case identification of CFS relies upon the

clinical assessment of a constellation of symptoms that have been present for

6 or more months since the onset of the fatiguing illness (Fukuda et al.,

1994). Since its emergence as a new disease category in the 1980s, four

definitions of CFS have been proposed, but none have been empirically derived

(Jason et al., 1997).

The current US case definition of CFS (Fukuda et al., 1994) requires that the

following criteria be met for diagnosis: (a) 6 or more months of persistent or

relapsing chronic fatigue of a new or definite onset that is neither the

result of ongoing exertion nor alleviated by rest, which results in

substantial reductions in previous levels of occupational, educational,

social, or personal activities; and (b) the concurrent occurrence of at least

four of eight symptoms (postexertional malaise, unrefreshing sleep, memory and

concentration difficulties, new headaches, sore throat, lymph node pain,

muscle pain, and joint pain) that persist or reoccur during 6 or more months

of the illness and do not predate the fatigue.

Researchers have sought to validate the criteria for CFS established by the

CDC using factor analytic methods. Nisenbaum et al. (1998) found that three

correlated factors (fatigue-mood-cognition symptoms, flu-type symptoms, and

visual impairment symptoms) explained a set of additional correlations between

fatigue lasting for 6 or more months and 14 inter-related symptoms. No factor

explained observed correlations among fatigue lasting for 1-5 months and other

symptoms, indicating that only fatigue lasting 6 or more months (with selected

symptoms) overlaps with published criteria to define CFS. In another study,

Friedberg et al. (2000) examined symptoms of patients with CFS who had an

illness duration of 10 or more years and found three factors: cognitive

problems, flu-like symptoms, and neurologic symptoms.

Other research has focused on classifying persons with CFS based on symptom

profiles. Using latent class analysis, Hadzi-Pavlovic et al. (2000) determined

that patients with CFS could be grouped into three classes: those with

multiple severe symptoms, those with lower rates of cognitive symptoms and

higher rates of pain; and those with a less severe form of multiple symptoms.

Participants with a less severe form of multiple symptoms tended to be younger

and with shorter illness duration. Jason and Taylor (2002) performed a cluster

analysis of persons in a community-based sample of persons with chronic

fatigue (fatigue lasting 6 or more months) to define a typology of chronic

fatigue symptomatology. Among the participants with CFS, findings suggested

that a majority of individuals with moderate to severe symptoms could be

classified into two important subgroups: one distinguished by severe

postexertional malaise with fatigue that was partially alleviated by rest; and

one distinguished by severe overall symptomatology, severe postexertional

malaise, and fatigue that was not alleviated by rest.

Researchers have also examined the occurrence of specific symptoms reported by

persons with chronic fatigue and CFS (Hartz and Komaroff). Komaroff et al.

(1996) examined the occurrence of minor symptoms (Holmes et al., 1988), as

well as respiratory, gastrointestinal, neurologic, rheumatologic, cardiac, and

miscellaneous objective and subjective symptoms that were not included in the

1988 case definition. The occurrence of these symptoms were compared among

persons with severe, disabling fatigue lasting for 6 or more months, persons

with multiple sclerosis, persons with major depression, and healthy controls.

Komaroff et al. (1996) concluded that rheumatologic and gastrointestinal

symptoms were found more frequently in patients meeting the major criteria.

Based upon these findings, researchers recommended adding anorexia and nausea

as well as eliminating the symptoms of muscle weakness, arthralgias, and sleep

disturbance to strengthen the case definition. Finally, Hartz et al. (1998)

examined the association between the number and severity of symptoms of CFS in

persons with idiopathic chronic fatigue and determined that persons with

fatigue could be classified by the degree to which they match the case

definition of CFS (Fukuda et al., 1994). In addition, Hartz et al. (1998)

suggested including symptoms such as frequent fever and chills, muscle

weakness, and sensitivity to alcohol in the current US case definition.

The occurrence of neurally mediated hypotension (NMH) has also been

investigated in persons with CFS. NMH is defined as a 30 mmHg drop in systolic

(or a 15 mmHg drop in diastolic) blood pressure in response to an orthostatic

challenge such as standing upright (Rowe and Calkins, 1998). This precipitous

drop in blood pressure is thought to be due to low blood volume (Streeten and

Bell, 1998) or excessive venous pooling in the extremities (Stewart and

Stewart). Symptoms of NMH include but are not limited to: lightheadedness,

dizziness when standing, nausea, fatigue, tremors, breathing or swallowing

difficulties, headaches, visual disturbances, and pallor (Streeten et al.,

2000). While the frequency of NMH in persons with CFS has not been

consistently reported across investigations, cardiopulmonary and neurological

abnormalities are heterogeneous and common (Wilke et al., 1998).

The findings reviewed herein suggest that other symptoms in addition to the

eight symptoms listed as part of the definitional criteria may be important

and occur frequently in persons with CFS. The present investigation examined

the occurrence of symptoms in the Fukuda et al. (1994) case definition of CFS

to determine whether these symptoms uniquely differentiated those with CFS

from controls. In addition, other fatigue/weakness related, sleep related,

neuropsychiatric, infectious, rheumatological, cardiopulmonary,

gastrointestinal, neurological, and reproductive symptoms not specified in the

current US case definition were examined. The occurrence of these additional

symptoms was examined to determine whether other symptoms occur with greater

frequency in persons with CFS when compared to controls, as well as what

symptoms occurred with greater frequency in the melancholic depression group

compared to controls.

2. Methods

2.1. PROCEDURE

The data are derived from a larger community-based study of the prevalence of

chronic fatigue syndrome (for more details of this study see Jason et al.,

1999). This larger study was carried out in three stages. Stage 1 involved

administering an initial telephone screening questionnaire in order to

identify the symptoms of chronic fatigue syndrome. Stage 2 involved

administering a semi-structured psychiatric interview. In stage 3,

participants underwent a complete physical examination. Following the

completion of the medical evaluation, four physicians and a psychiatrist were

responsible for making a final diagnosis with two physicians independently

rating each case using the current US case definition of CFS (Fukuda et al.,

1994). Where disagreement occurred, a third physician rater was used.

2.2. SAMPLE

Procedures developed by Kish (1965) were used to select one adult from each

household. Birth dates for each adult were gathered, and the person with the

most recent birthday was selected for interview. A stratified random sample of

several neighborhoods in Chicago was utilized (see Jason et al., 1999 for more

details). In stage 1, 28,673 residential/working telephone numbers were

contacted, and 18,675 adults completed the initial screening interview (65.1%

completion rate).

The stage 1 screen revealed that of the 18,765 participants who were

interviewed, 780 (4.2%) had chronic fatigue. Of these, 408 had chronic fatigue

and the concurrent occurrence of four or more symptoms. These participants

were defined as CFS-like (the suffix `like’ was used to clarify that

individuals in this group only met the Fukuda et al. (1994) criteria by

self-report, and did not necessarily qualify as having a final diagnosis of

CFS rendered by a physician).

One hundred and sixty-six of the 408 CFS-like participants agreed to complete

a structured psychiatric interview and a comprehensive physical examination.

There were no significant differences on sociodemographic (i.e. gender, ethnic

identification, age, occupation, education, and marital status) or fatigue

scores between these 166 screened positive (CFS-like) participants and the 242

screened positive (CFS-like) non-participants. The control group was composed

of 199 individuals selected randomly from the remaining 18,260 screened

negatives (seven cases were excluded due to missing data). Of these 199

individuals, 47 completed medical evaluations. There were no sociodemographic

differences (i.e. gender, ethnic identification, age, occupation, education,

and marital status) or fatigue scores between the 152 screened negative

non-participants and 47 screened negative participants. Participants were then

classified by independent physician consensus.

2.3. PARTICIPANTS

The present investigation examined the occurrence of symptoms in three groups

of participants. The first group consisted of 32 persons from the larger group

of 166 persons with CFS-like symptoms who were diagnosed with CFS by the

independent physician review panel (CFS group). The second group consisted of

19 individuals with melancholic depression, who were taken from a larger group

of 33 CFS-like persons with a psychiatric explanation for their chronic

fatigue illness (Melancholic Depression group). Melancholic Depression was

diagnosed using the Structured Clinical Interview for the DSM-IV (SCID)

(Spitzer et al., 1995), which is a valid and reliable semi-structured

interview guide that approximates a traditional psychiatric interview.

Melancholic Depression is defined by either the absence of pleasure in almost

all activities or lack of reactivity to usually pleasurable stimuli. In

addition, there would need to be three or more other symptoms, such as

excessive guilt, significant weight loss, and marked psychomotor retardation

or agitation. The control group consisted of 47 randomly selected individuals

who screened negative for having a CFS-like illness (control group). Three

participants who initially screened negative for a CFS-like illness were

excluded from the control group following examination by the study physicians

who determined that they had idiopathic chronic fatigue or chronic fatigue

explained by a psychiatric condition.

2.4. MEASURES

2.4.1. Medical questionnaire

As part of a detailed medical questionnaire, participants were asked if they

were experiencing or had experienced each of the eight Fukuda et al. (1994)

symptoms of CFS in the past 6 months. Additional symptoms examined included

other medical symptoms and neuropsychiatric symptoms that incorporated

questions from a measure used by Komaroff et al. (1996). The definitional

symptoms and the additional symptoms were then classified into the following

categories: weakness/fatigue, disturbed sleep, neuropsychiatric, infectious,

rheumatological, cardiopulmonary, neurological, and reproductive

abnormalities. We examined the occurrence of Fukuda et al. (1994) symptoms in

the past 6 months because it was most comparable to available data on the

occurrence of other symptoms examined in the medical questionnaire. Also,

examining the occurrence of Fukuda et al. (1994) defined symptoms in the past

6 months allows results of the present investigation to be compared to those

of Komaroff et al. (1996).

2.5. STATISTICAL ANALYSES

First, the sociodemographic variables of gender, age, ethnicity, marital

status, parental status, work status, and socioeconomic status were examined,

using chi-squares across the three groups: CFS, melancholic depression, and

controls. The occurrence of symptoms was compared between the CFS and control

groups, and between the melancholic depression and control groups. Using

binomial logistic regression, sociodemographic variables that were found to be

significant between the groups were entered as predictors in the logistic

regression model to control for the effects of these variables on the

occurrence of symptoms. We first made the CFS group the referent group, and

have compared it to the controls and the depression group. We next made the

control group as a referent group to compare it with the depressed group. Due

to the numerous comparisons made, the overall statistical significance was set

at P<0.01 for all analyses in order to minimize the likelihood of type I

error.

3. Results

3.1. SOCIODEMOGRAPHIC VARIABLES

Analyses indicated that there were significantly more men in the control group

than in the Melancholic Depression group [chi^2(2,95)=11.297, P<0.01].

Furthermore, participants with CFS were significantly more likely to have

children than controls [chi^2(2,95)=9.431, P<0.05]. Thus, gender and parental

status were entered as predictors in the subsequent binomial logistic regression

analyses of symptom occurrence.

3.2. SYMPTOMS

Table 1 presents symptoms of Fatigue/Weakness, Disturbed Sleep,

Neuropsychiatric, Infectious, and Rheumatological symptoms, and these are the

symptom categories in which are located the current Fukuda et al. (1994) CFS

symptom criteria. Table 2 lists other categories (Cardiopulmonary,

Gastrointestinal, Neurological, and Reproductive) that consist of symptoms

that are not found within the Fukuda et al. (1994) criteria.

3.2.1. Fatigue/weakness

Participants with CFS differed significantly from controls in the occurrence

of generalized muscle weakness, and more specific weakness in their legs,

arms, neck, and back. Weak legs was the most frequently reported form of

weakness for the CFS group. Also, participants with CFS and those with

melancholic depression both reported significantly more postexertional malaise

than controls.

3.2.2. Disturbed sleep

The occurrence of unrefreshing sleep was reported with significantly greater

frequency in both the CFS and melancholic depression groups compared to

controls. Those in the CFS group had significantly more insomnia than the

controls.

3.2.3. Neuropsychiatric

Participants with CFS reported the occurrence of new headaches with

significantly greater frequency than controls. Both the CFS and melancholic

depression groups reported the occurrence of memory and concentration

difficulties, depression, and irritability with significantly greater

frequency than controls.

3.2.4. Infectious

The occurrence of sore throats and lymph node pain was significantly greater

in the CFS group when compared to controls. There were no significant

differences between the melancholic depression and control groups in the

occurrence of other infectious symptoms.

3.2.5. Rheumatological

The CFS group reported muscle pain, joint pain, morning stiffness, and hay

fever with significantly greater frequency than controls. Participants with

melancholic depression only reported the occurrence of dry mouth with

significantly greater frequency than controls.

3.2.6. Cardiopulmonary

The CFS group reported the occurrence of chest pain and cough with

significantly greater frequency than controls. The CFS group and melancholic

depression group significantly differed on shortness of breath.

3.2.7. Gastrointestinal

Neither the CFS nor the melancholic depression groups reported

gastrointestinal symptoms with significantly greater frequency than controls.

3.2.8. Neurological

The CFS group reported dizziness after standing, skin sensations, general

dizziness, alcohol intolerance and dizzy moving head with significantly

greater frequency than controls.

3.2.9. Reproductive

Participants with CFS reported the occurrence of decreased sexual interest

with significantly greater frequency than controls and those with melancholic

depression. The occurrence of impairment of sexual functioning was reported

with significantly greater frequency in both the CFS and melancholic

depression groups when compared to controls.

4. Discussion

Results of this investigation lend support to the importance of the CFS

diagnostic criteria (Fukuda et al., 1994). Participants with CFS more

frequently experienced the Fukuda et al. (1994) CFS symptoms when compared to

other symptoms in their respective categories, with the exception of

postexertional malaise. These findings were anticipated, given the selection

criteria of four of eight symptoms to receive a diagnosis of CFS. In addition,

the CFS group in comparison to controls reported significantly higher

frequencies of all eight Fukuda et al. (1994) definitional symptoms.

Furthermore, the occurrence of postexertional malaise, cognitive and memory

difficulties and unrefreshing sleep did not uniquely discriminate between the

CFS and control groups, as individuals in the melancholic depression group

also experienced these symptoms with significantly greater frequency than

controls.

Interpreting these findings, it is important to note that the present

investigation examined only the occurrence of symptoms. The CFS group may also

uniquely differ from controls in symptom duration and severity. For example,

Jason et al. (2000) found that examining symptoms utilizing severity

criteria has proven useful in uniquely differentiating CFS from fatigue

explained by a psychiatric disorder (Jason et al., 2000). Also, the frequency

of the occurrence of the Fukuda et al. (1994) defined symptoms in the

melancholic depression group may have been elevated due to the screening

process. Only chronically fatigued participants initially reporting four or

more symptoms specified in the current US case definition of CFS were

classified as `CFS-like’ and subsequently received a medical examination.

Cardiopulmonary and neurological abnormalities have been investigated as they

relate to neurally mediated hypotension (NMH) in persons with CFS (Rowe;

Streeten and Wilke). NMH occurs when the central nervous system

misinterprets the body’s needs when it is in an upright position, then sends a

message to the heart to slow down and lower the blood pressure, responses that

are directly opposite to the responses the body`s needs. Several

cardiopulmonary and neurological symptoms in the present investigation

occurred with higher frequency and uniquely differentiated the CFS group from

controls. Shortness of breath, chest pain, dizziness after standing, skin

sensations, general dizziness, dizzy moving the head, and alcohol intolerance

uniquely differentiate those with CFS from controls. It is possible that

examining these cardiopulmonary and neurological abnormalities not currently

assessed by the current case definition (Fukuda et al., 1994) could provide

greater diagnostic reliability.

The CFS and melancholic depression group only significantly differed for two

symptoms: decreased sexual interest and shortness of breath. Decreased sexual

interest might very well be a result of low levels of cortisol. A deficit of

cortisol has been found in patients with CFS, and is linked to lethargy and

fatigue, and this deficit might be contributing to an overactive immune system

(Scott and Dinan, 1999). Shortness of breath as well as other neurological

symptoms might reflect a finding that has been confirmed by other

investigators, who have not found neurally mediated hypotension to play a

major role in CFS (Poole et al., 2000).

Komaroff et al. (1996) have suggested that eliminating the symptoms of muscle

weakness, arthralgias, and sleep disturbance would provide greater sensitivity

and specificity in CFS diagnosis. In contrast, the present investigation found

that muscle weakness and arthralgias were reported in over half of

participants with CFS and uniquely differentiated this group from controls.

Regarding sleep disturbance, results of the present investigation did not

support the ability of any symptoms in this category to uniquely discriminate

between CFS and control groups. Komaroff et al. (1996) also suggested adding

anorexia and nausea as minor symptoms in the CFS case definition. However, in

the present study, both occurred with relatively low frequency and neither

uniquely differentiated those with CFS from controls.

Hartz et al. (1998) also investigated the occurrence of symptoms in persons

with fatigue, and recommended the inclusion of fever and chills, muscle

weakness, and sensitivity to alcohol as CFS case definition symptoms. Results

of the current investigation also indicated that muscle weakness and

sensitivity to alcohol uniquely differentiated the CFS group from controls,

but neither the CFS nor the melancholic depression groups significantly

differed from controls in the occurrence of fever and chills. Furthermore, it

appeared that muscle weakness in the CFS group occurred at multiple sites,

with weak legs being the most frequently reported form of weakness. These

findings concur with those of Hartz et al. (1998), and therefore provide

further support for the inclusion of muscle weakness in the case definition of

CFS.

Differences between the present investigation and previous work could be a

result of the sampling methods employed. Other research has relied on

predominantly clinic-based samples that may report greater occurrence and

severity of symptoms, especially those of a viral or infectious nature

(Wessely, 1998). Persons with CFS found in clinic-based samples may

represent a more severely ill population. Current findings should be

interpreted within the context of limitations on statistical power imposed by

a small sample size. Small sample sizes might have precluded the detection of

significant differences between groups, and this may be especially true for

all comparisons with the depressed group because they have the smallest sample

size and because they appear to be mid-way on most measures between the CFS

group and controls. Because some differences between groups may have not been

detected, more research with larger samples is necessary to replicate these

results.

In summary, results from this investigation in a community-based sample

support the use of the symptoms included in the current CFS case definition

(Fukuda, et al., 1994). Furthermore, this investigation found that weakness

and various neurological, cardiopulmonary, neuropsychiatric, and

rheumatological symptoms uniquely differentiated persons with CFS from the

control group. In contrast, relatively few of these symptoms significantly

differentiated the group of individuals with melancholic depression from the

control group.

Acknowledgements

Financial support for this study was provided by NIAID grant number AI36295.

Requests for reprints should be sent to Leonard Jason, Ph.D., Center for

Community Research, DePaul University, 990 W. Fullerton Ave. Chicago, IL

60614.

Tables

Table 1. Occurrence of symptoms in Fukuda Symptom Categories

————————————————————————

CFS Melancholic No Significance

Depression Fatigue

(N=32) (N=19) (N=44)

% % %

————————————————————————

Fatigue/weakness

General muscle 75.0 a 47.4 18.2 **

weakness

Postexertional 68.8 a 47.4 13.6 **

malaise

Legs weak 62.5 a 26.3 9.1 **

Arms weak 53.1 a 26.3 11.4 **

Neck weak 40.6 a 21.1 4.5 **

Shoulders weak 40.6 21.1 6.8

Back weak 40.6 a 15.8 9.1 **

Head weak 25.0 5.3 2.3

Abdomen weak 9.4 5.3 0.0

Buttocks weak 3.1 0.0 0.0

Other weak muscles 3.1 15.8 0.0

Disturbed sleep

Unrefreshing sleep 90.6 a 84.2 25.0 **

Insomnia 59.4 a 36.8 15.9 **

Early morning 59.4 47.4 25.0

awakening

Trouble staying 43.8 21.1 11.4

asleep

Hypersomnia 31.3 42.1 22.7

Neuropsychiatric

Memory and 87.5 a 63.2 b 20.5 **

concentration

New headaches 75.0 a 68.4 31.8 **

Depression 56.3 a 73.7 b 13.6 **

Irritability 50.0 a 42.1 b 11.4 **

Disturbances in 46.9 26.3 11.4

eyesight

Infectious

Sore throat 62.5 a 42.1 29.5 **

Lymph pain 40.6 a 21.1 9.1 **

Fever/chills 21.9 15.8 9.1

Oral herpes 6.3 21.1 9.1

Shingles 3.1 0.0 4.5

Oral thrush 3.1 5.3 0.0

Genital herpes 0.0 15.8 0.0

Rheumatological

Muscle pain 84.4 a 52.2 22.7 **

Joint pain 56.3 a 26.3 20.5 **

Morning stiffness 56.3 a 36.8 15.9 **

Stiff after sitting 56.3 a 31.6 25.0

Hay fever 46.9 a 42.1 13.6 **

Puffy face 40.6 21.1 11.4

Dry mouth 37.5 57.9 b 11.4 **

Night sweats 34.4 15.8 0.0

Sinus infection 31.3 21.1 9.1

Earaches 25.0 31.6 6.8

Dry eyes 21.9 15.8 9.1

Eye pain 21.9 5.3 9.1

Jaw pain 18.8 10.5 0.0

————————————————————————

Italics indicate symptoms that are part of the current CFS case definition

(Fukuda et al., 1994).

a Statistically significant difference between CFS and No Fatigue groups.

b Statistically significant difference between Melancholic Depression and

No Fatigue groups.

** Using binomial logistic regression analyses, difference is statistically

significant at the P<0.01 level.

Table 2. Occurrence of symptoms in Non-Fukuda Symptom Categories

————————————————————————

CFS Melancholic No Significance

Depression Fatigue

(N=32) (N=19) (N=44)

% % %

————————————————————————

Cardiopulmonary

Shortness of breath 65.6 a 26.3 c 22.7 **

Chest pains 40.6 a 10.5 6.8 **

Rapid heartbeat 34.4 15.8 9.1

Cough 28.1 a 26.3 2.3 **

Heartbeat in ears 18.8 21.1 2.3

Raynaud’ phenomenon 9.4 10.5 2.3

Gastrointestinal

Bloating 40.6 26.3 9.1

Lower abdominal 37.5 21.1 9.1

pain

Upper abdominal 31.3 21.1 9.1

pain

Anorexia 28.1 15.8 9.1

Nausea 25.0 21.1 0.0

Diarrhea 12.5 5.3 6.8

Black bowel movement 9.4 5.3 0.0

Blood in bowel 9.4 15.8 2.3

movement

Neurological

Dizzy after 46.9 a 21.1 9.1 **

standing

Skin sensations 46.9 a 21.1 9.1 **

General dizziness 43.8 a 36.8 2.3 **

Alcohol intolerance 43.8 a 15.8 6.8 **

Dizzy moving head 37.5 a 15.8 6.8 **

Unsteady upright 28.1 21.1 6.8

Ringing in ears 21.9 31.6 11.4

Tingling sensations 15.6 5.3 0.0

Paralysis 3.1 0.0 0.0

Temporary blindness 6.3 0.0 0.0

Reproductive

Decreased sexual 50.0 a 15.8 c 6.8 **

interest

Impairment of 50.0 a 36.8 b 2.3 **

sexual functioning

Nocturia 43.8 31.6 13.6

Irregular periods d 37.5 52.9 61.9

Incontinence 21.9 10.5 6.8

Menopause d 20.8 11.8 23.8

Vaginal discharge d 20.8 35.3 19.0

Excessive menstrual 16.7 17.6 0.0

bleeding d

Recurrent urinary 12.5 5.3 2.3

infections

Recurrent vaginal 6.3 10.5 2.3

infections d

Dysuria 6.3 0.0 0.0

Nipple discharge d 4.2 5.9 0.0

Positive pap smear d 0.0 0.0 4.8

Blood in urine 0.0 0.0 0.0

————————————————————————

a Statistically significant difference between CFS and No Fatigue groups.

b Statistically significant difference between Melancholic Depression and

No Fatigue groups.

c Statistically significant difference between the CFS and Melancholic

depression groups.

d Women only.

** Using binomial logistic regression analyses, difference is statistically

significant at the P<0.01 level.

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