Applied Neuropsychology Copyright 2001 by

2001, Vol. 8, No. 1, 41–50 Lawrence Erlbaum Associates, Inc.

Longitudinal Assessment of Neuropsychological Functioning,

Psychiatric Status, Functional Disability and Employment Status in
Chronic Fatigue Syndrome LONGITUDINAL ASSESSMENT IN CHRONIC FATIGUE
TIERSKY
SYNDROME
ET AL.

Lana A. Tiersky
School of Psychology, Fairleigh Dickinson University, Teaneck, New Jersey, USA,
Department of Physical Medicine and Rehabilitation, University of Medicine and Dentistry
of New Jersey, New Jersey Medical School, Newark, New Jersey, USA, and Chronic
Fatigue Syndrome Center, Newark, New Jersey, USA
John DeLuca
Department of Physical Medicine and Rehabilitation, University of Medicine and Dentistry
of New Jersey, New Jersey Medical School, Newark, New Jersey, USA, Chronic Fatigue
Syndrome Center, Newark, New Jersey, USA, and Kessler Medical Research, Rehabilitation
and Education Corporation, West Orange, New Jersey, USA
Nancy Hill
Chronic Fatigue Syndrome Center, Newark, New Jersey, USA
Sunil K. Dhar
Department of Mathematical Sciences and the Center for Applied Mathematics and
Statistics, New Jersey Institute of Technology, Newark, New Jersey, USA
Susan K. Johnson
Department of Psychology, University of North Carolina-Charlotte, Charlotte, North
Carolina, USA
Gudrun Lange
Chronic Fatigue Syndrome Center, Newark, New Jersey, USA, and Departments of
Radiology and Psychiatry, University of Medicine and Dentistry of New Jersey, New Jersey
Medical School, Newark, New Jersey, USA
Gabrielle Rappolt
Chronic Fatigue Syndrome Center, Newark, New Jersey, USA
Benjamin H. Natelson
Chronic Fatigue Syndrome Center, Newark, New Jersey, USA, and Department of
Neurosciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical
School, Newark, New Jersey, USA

The longitudinal course of subjective and objective neuropsychological functioning, psycho-

logical functioning, disability level, and employment status in chronic fatigue syndrome (CFS)
was examined. The relations among several key outcomes at follow-up, as well as the baseline

This research was supported by Grants U0I–AI32247 and R01–MH52810 from the National Institutes of Health.
Requests for reprints should be sent to Lana A. Tiersky, School of Psychology, Fairleigh Dickinson University, 1000 River Road, Mail Stop
T-WH1-01, Teaneck, NJ 07666, USA.

41
 TIERSKY ET AL.

characteristics that predict change (e.g., improvement), were also evaluated. The study sample
consisted of 35 individuals who met the 1988 and 1994 CFS case definition criteria of the Cen-
ters for Disease Control (CDC) at intake. Participants were evaluated a mean of 41.9 (SEM =
1.7) months following their initial visit (range = 24–63 months). Results indicated that objec-
tive and subjective attention abilities, mood, level of fatigue, and disability improve over time in
individuals with CFS. Moreover, improvements in these areas were found to be interrelated at
follow-up. Finally, psychiatric status, age, and between-test duration were significant predic-
tors of outcome. Overall, the prognosis for CFS appears to be poor, as the majority of partici-
pants remained functionally impaired over time and were unemployed at follow-up, despite the
noted improvements.

Key words: chronic fatigue, neuropsychological assessment, follow-up

Although numerous cross-sectional studies docu-
ment the extent and nature of cognitive impairment,
psychological distress, disability, and unemployment
in chronic fatigue syndrome (CFS), it remains unclear
how these factors change over time (Tiersky, Johnson,
Lange, Natelson, & DeLuca, 1997; Wessely, Hotopf, &
Sharpe, 1998). Few longitudinal studies have been
completed, and even fewer have used CFS samples de-
fined by recognized clinical criteria (Joyce, Hotopf, &
Wessely, 1997). Thus, the purpose of this investigation
was to evaluate these variables over time in a group of
CFS patients diagnosed according to case definition
criteria.
A key feature of CFS is subjective and objective
cognitive impairment. It is estimated that between 74%
and 95% of CFS patients complain of some type of cog-
nitive deficit (Komaroff & Buchwald, 1991; Vercoulen
et al., 1998). In addition, studies of objective
neuropsychological functioning in CFS consistently
document impairment in information-processing
speed, divided auditory attention, and memory (for re-
views, see DiPino & Kane, 1996; Moss-Morris, Petrie,
Large, & Kydd, 1996; Tiersky et al., 1997).
Given its centrality, it is important to examine the
longitudinal course of cognitive functioning in CFS, as
it likely affects the overall prognosis of the illness.
Only two longitudinal studies have examined change in
subjective or objective cognitive abilities in individuals
diagnosed with CFS or chronic fatigue. One study in-
vestigated cognitive functioning in 14 patients with
chronic fatigue over the course of an average of 6
months. In this study, chronic fatigue was defined as
scoring above a certain cutoff point on a measure of fa-
tigue and demonstrating fatigue for at least 6 months.
Although limited by the small sample size and short du-
ration of follow-up, this study found that the patients
significantly improved on a block design task, a
supraspan learning task, and a verbal paired associates
task (Cope, Pernet, Kendall, & David, 1995). In the
second study, Vercoulen et al. (1996) found that sub-
jective concentration difficulties significantly de-
creased over time in individuals who rated themselves
as recovered from CFS or generally improved. Clearly,
little is known about the longitudinal course of subjec-
tive and objective cognitive impairment in CFS.
When examining the course of an illness, it is impor-
tant to look at factors that affect prognosis. Although no
study has investigated the effect of baseline level of ob-
jective neuropsychological impairment on final out-
come, two studies have investigated how initial level of
subjective cognitive impairment affects prognosis
(Ray, Jefferies, & Weir, 1997; Vercoulen et al., 1996).
The findings of these studies are mixed. One study re-
ported that higher scores on a measure of cognitive
problems at baseline predicted higher levels of fatigue
at follow-up (Ray et al., 1997). Vercoulen et al. (1996),
however, did not find that baseline level of cognitive
difficulty affected prognosis. In addition, it remains an
open question whether objective neuropsychological
abilities affect outcome. It is possible that objective
neuropsychological abilities contribute to overall prog-
nosis in CFS, because neuropsychological impairment
was found to be related to functional disability in a
cross-sectional study (Christodoulou et al., 1998).
Psychiatric comorbidity is common in CFS
(Wessely et al., 1998), but its status over time has not
been extensively investigated. One study that examined
the natural course of CFS found that self-reported
symptoms of depression and general psychological
well-being significantly improve over time in some
CFS patients (Vercoulen et al., 1996). Although few
studies have examined the course of psychiatric distur-
bance in CFS, several have attempted to relate psychi-
atric status at baseline to health status at follow-up. The
majority of studies have found that psychological status
at initial evaluation is not related to improvement in

42
 LONGITUDINAL ASSESSMENT IN CHRONIC FATIGUE SYNDROME
CFS symptoms, fatigue, or self-rated functional im-
pairment at outcome (Hill, Tiersky, Scavalla, Lavietes,
& Natelson, 1999; Ray et al. 1997; Vercoulen et al.,
1996; Wilson et al., 1994). Bombardier and Buchwald
(1995), however, found that having a dysthymic disor-
der at initial evaluation predicted general improvement
but accounted for only 2% of the variance. Moreover,
studies that have looked at the relation between general
improvement and psychiatric status at follow-up have
found that improvement in health status is related to im-
provement in psychiatric functioning (Hill et al., 1999;
Vercoulen et al., 1996; Wilson et al., 1994). Thus, we
know little about the longitudinal course of psychiatric
symptoms in CFS other than that as health status im-
proves, psychiatric status does as well.
Functional disability is also often observed in CFS,
but only a few authors have examined the course of dis-
ability over time (Ray et al., 1997; Vercoulen et al.,
1996; Wilson et al., 1994). In general these studies
show that although functional disability tends to signif-
icantly improve, many patients remain disabled at fol-
low-up. For instance, Wilson et al. found that at
follow-up 32% of participants were unable to perform
any significant physical activity and Vercoulen et al.
found that at follow-up only 3% of the total sample was
performing at the level of healthy participants on a
measure of functional ability. In addition, studies that
have examined the factors that predict disability in CFS
conclude that illness duration, levels of baseline fatigue
(Ray et al., 1997), as well as baseline scores on mea-
sures of illness beliefs such as “disease conviction” are
related to functional impairment at follow-up (Wilson
et al., 1994). Thus, it appears that individuals with CFS
remain disabled over time and that illness beliefs, ill-
ness duration, and initial fatigue level play some role in
this outcome.
Although unemployment is common in CFS
(Wessely et al., 1998), only two studies have examined
employment status over time in individuals with CFS.
Both Hill et al. (1999) and Vercoulen et al. (1996)
found no significant change in employment status from
baseline to follow-up in individuals with CFS. More-
over, little is known about what predicts employment
status at follow-up. Specifically, Bombardier and
Buchwald (1995) found that demographic, clinical, or
psychiatric variables were not predictive of return to
work. Thus, it appears that employment status does not
change in CFS over time. Still, the baseline factors that
contribute to this outcome are not yet identified.
The purpose of this investigation was to examine
change in subjective and objective neuropsychological
functioning, psychological functioning, disability sta-
tus, and employment status in CFS over the course of
several years. Change in CFS severity and fatigue was
also examined to provide descriptive information per-
taining to severity of illness in the sample. In addition
to examining change over time, the baseline character-
istics that predict improvement in objective
neuropsychological functioning and disability, as well
as employment status at follow-up, were evaluated.
Finally, the relations among key outcomes were studied
to determine if long-term performances were interre-
lated. Thus, we also investigated the relations among
neuropsychological functioning, disability level, fa-
tigue, and mood at follow-up.
Method
Participants
At study entry, 47 individuals who were participants
in the New Jersey Fatigue Research Center and who
completed a comprehensive neuropsychological and
psychological evaluation were invited to participate in
the longitudinal investigation. In addition to meeting
the 1988 and 1994 CFS case definition, participants
also had to meet the following inclusion and exclusion
criteria at study entry: (a) onset of CFS within the 4
years prior to the initial evaluation, (b) presence of
symptoms of at least moderate severity at intake, (c) no
history of psychiatric disorder in the 5 years prior to in-
take, (d) no substance abuse history, and (e) no loss of
consciousness greater than 5 min.
All 47 individuals who participated in the initial
baseline evaluation (Time 1) were later contacted to
participate in the follow-up psychological and
neuropsychological evaluations (Time 2). The follow-
ing procedures were utilized to contact patients at Time
2. First, all participants who participated at Time 1 were
contacted by phone to schedule an appointment for the
Time 2 evaluation. Participants who were unable to re-
turn in person at Time 2, but who were willing to partic-
ipate in the study, were sent questionnaire measures to
complete. Individuals who were unwilling to partici-
pate at Time 2, as well as those who could not be
reached by phone, were sent a follow-up letter to re-
quest participation. Those individuals who could not be
contacted or who refused to participate were consid-
ered lost to follow-up or nonresponders.
Of those participants contacted, 35 (74.5%) partici-
pated at Time 2. These participants were designated as
responders. Two responders (4%) only completed
questionnaire measures that allowed us to rate CFS se-
43
 TIERSKY ET AL.
verity because they lived geographically too distant to
complete the in-person evaluations. Twelve (25.5%) of
the 47 individuals declined to participate or could not
be contacted and were designated nonresponders. Par-
ticipants were reevaluated a mean of 41.9 (SEM = 1.7)
months following their initial visit (range = 24–63
months).
At Time 1, the mean age of the responders was 35.5
(SEM = 1.6) years, the mean level of education was
14.8 (SEM = .40) years, and the mean duration of ill-
ness was 25.9 (SEM = 2.5) months. At Time 2, the
mean age of the responders was 38.9 (SEM = 1.5) years,
and the mean educational level, which did not signifi-
cantly change over time (p > .05), was 14.8 (SEM = .40)
years. Some of the individuals who participated in this
investigation were also included in an earlier investiga-
tion of longitudinal functioning in CFS (Hill et al.,
1999).
Procedure
Initial baseline evaluation (Time 1). At Time 1,
all participants underwent a comprehensive psycholog-
ical and physical assessment. During the physical as-
sessment, a medical history was obtained by a physi-
cian’s assistant or nurse practitioner trained in the
diagnosis of CFS. At this time, the severity of each indi-
vidual’s CFS was rated by the clinician using a 6-point
scale. The CFS severity category rankings are listed in
Table 1. CFS severity was rated based on level of reduc-
tion in activity and number and severity of minor symp-
toms rated from 0 (symptom is no problem) to 5 (symp-
Table 1. CFS Severity Rating Scale
Rating Definition of Numeric Rating
1 ≥ 50% reduction in activity and 7 symptoms rated as
at least substantial (severe CFS)
2 ≥ 50% reduction in activity and 4–6 symptoms rated
as at least substantial
3 < 50% reduction in activity and 4 or more symptoms
rated as at least substantial (at least 3 symptoms
rated as very severe)
4 < 50% reduction in activity and 4 or more symptoms
rated as at least substantial (no more than 2
symptoms may be rated as very severe)
5 ≥ 50% reduction in activity (must be at least
substantial) and 4 or more symptoms rated less
than substantial
6 Substantial reduction in activity and 4 or more
symptoms rated less than substantial
Note: CFS = chronic fatigue syndrome.
44
tom is a very severe problem). Information pertaining to
psychiatric status was obtained using the Quick Diag-
nostic Interview Schedule for the Diagnostic and Statis-
tical Manual of Mental Disorders (3rd ed., rev.
[DSM–III–R]; American Psychiatric Association,
1987), a structured computerized diagnostic interview
that was administered by trained personnel (Marcus,
Robins, & Bucholz, 1990). A psychiatric disorder was
considered concurrent if the onset of the disorder oc-
curred following the onset of CFS. Thus, participants
who were diagnosed with a concurrent Axis I disor-
der(s) at Time 1 were noted to have the disorder concur-
rent with CFS. In addition, lifetime history of psychiat-
ric illness was also evaluated. Axis II status was
determined based on the participants’ responses on the
Personality Diagnostic Questionnaire–Revised, which
is a self-report questionnaire (Hyler & Rieder, 1987).
At Time 1, participants also completed a
neuropsychological evaluation that included the fol-
lowing measures: The California Verbal Learning Test
(CVLT; Delis, Dramer, Kaplan, & Ober, 1987); the
Paced Auditory Serial Addition Task (PASAT;
Gronwall, 1977); the Rey–Osterreith Complex Figure
Test, Immediate Recall (ROCF–I) and Delayed Recall
(ROCF–D) subtests (Corwin & Bylsma, 1993); the
Wechsler Adult Intelligence Scale–Revised (WAIS–R)
Digit Span Forward and WAIS–R Digit Span Back-
ward subtests (Wechsler, 1981); the Meta-Memory
Questionnaire (Mateer, Sohlberg, & Crinean, 1987);
the Beck Depression Inventory (BDI; Beck, Ward,
Medelson, Mock, & Erbaugh, 1961); and the
State–Trait Anxiety Inventory–Form X (Spielberger,
Gorsuch, & Lushene, 1983). All measures were admin-
istered according to published procedures.
In addition, at Time 1 participants completed the Fa-
tigue Rating Scale (Krupp, LaRocca, Muir-Nash, &
Steinberg, 1989), which is a self-report measure. A
self-report measure of magnitude of disability due to
illness, the CFS Disability Scale (CDS), was also com-
pleted. The CDS is a modification of the Karnofsky
Performance Index (Wilson et al., 1994) in which the
areas of mild to moderate disability are expanded.
Moreover, it uses a scoring system whereby each dis-
ability rating is defined within a 10-point band. The
CDS has been utilized in other studies examining func-
tional ability in CFS (Natelson et al., 1995). Employ-
ment status (i.e., employed full time or part time or
unemployed or retired due to health) was also deter-
mined during the initial evaluation.
Follow-up evaluation (Time 2). All participants
who returned in person at Time 2 underwent both a
 LONGITUDINAL ASSESSMENT IN CHRONIC FATIGUE SYNDROME
physical assessment and a neuropsychological evalua-
tion. At this time, a follow-up psychiatric interview was
completed, and a follow-up medical history was also
obtained. The procedures for administration of the Time
2 assessments were the same as those followed at Time
1 except that lifetime history of disease or
psychopathology was not reassessed during the medical
history and psychiatric interview. A trained physician’s
assistant or nurse practitioner rated CFS severity during
the follow-up evaluation.
Analyses
Due to the non-normal distributions of the data,
Wilcoxon matched-pair sign-rank tests were used to ex-
amine the significance of change over time for the con-
tinuous variables. McNemar’s binomial probability test
was utilized to examine change over time for the dichot-
omous variables. When normality assumptions for two
independent samples were not satisfied, Mann–Whitney
U tests were utilized to compare group differences
within Time 1. A proportion test (the Z test) was used to
examine improvement in CFS severity. Because the
sample size was large (n > 30), the Central Limit Theo-
rem was invoked to validate the use of the Z test.
Spearman’s rank correlation coefficients were com-
puted to determine the level of association among the
variables because they were non-normal in distribution
as well.
Logistic regression analyses were completed to pre-
dict improvement in disability level and
neuropsychological functioning, as well as employ-
ment status at Time 2. Improvement in disability was
defined as a 10-point decrease in disability level as
measured by the CDS. The improved group, therefore,
consisted of participants whose CDS scores improved
by at least 10 points at Time 2. Those participants who
did not demonstrate such an improvement were consid-
ered not improved. Ten points was chosen as the crite-
ria for improvement because each 10-point band of
scores on the CDS defines a different disability cate-
gory. Improvement in neuropsychological functioning
was defined as a 1-point decrease on the impairment in-
dex from Time 1 to Time 3. Thus, participants who de-
creased by 1 point on the impairment index from Time
1 to Time 2 were placed in the improved category, and
those that did not demonstrate such a decrease in im-
pairment were considered not improved.
Improvement in CFS severity was defined as a
1-point increase in CFS category (i.e., a lessening of
symptoms). Thus, those participants who improved by at
least 1 point from Time 1 to Time 2 on the measure of cli-
nician-rated CFS severity were placed in the improved
category, and those that did not demonstrate any positive
change in symptoms were categorized as not improved.
The following were used as predictor variables in all
of the regression analyses: duration of illness, illness se-
verity, duration of time lapsed between baseline and fol-
low-up evaluation (“between test duration”), presence
of a concurrent psychiatric diagnosis, age, gender, and
education at Time 1. To predict improvement in level of
neuropsychological functioning, also included in the
model was disability status at Time 1. To predict im-
provement in disability status, level of
neuropsychological impairment at Time 1 was also in-
cluded. Finally, to predict employment status at Time 2,
level of neuropsychological impairment and disability
status at Time 1 were included in the model. A backward
stepwise elimination method was used to complete all of
the logistic regression analyses. Specifically, all of the
predictor variables were included in the initial model.
Then, the variable whose coefficient was the least signif-
icant, including that of the constant, was removed from
the model one step at a time.
To examine overall neuropsychological function-
ing, a neuropsychological impairment index was cre-
ated that was similar to that utilized in other studies of
cognitive functioning in CFS (Christodoulou et al.,
1998). This index was created by summing the number
of tests a participant failed. A test was considered failed
if the individual performed 2 or more SD below the
mean of a healthy control group on a given test. The
data on the healthy comparison group have been pub-
lished elsewhere (DeLuca, Johnson, Beldowicz, &
Natelson, 1995). The measures included in the index
were the following: CVLT total score (CVLT–T),
long-delay free recall (CVLT–LDF), and short-delay
free recall (CVLT–SDF); PASAT total score; ROCF–I
and ROCF–D; and WAIS–R Digit Span Forward and
WAIS–R Digit Span Backward subtests.
Results
Comparison Between Responders and
Nonresponders on Time 1 Measures
To examine for the possibility of a sampling bias,
the Time 1 performance of the responders (n = 35) was
compared to those who did not respond
(nonresponders, n = 12). There were no significant dif-
ferences in age, education, illness severity, illness dura-
tion, employment status, gender, level of depression, or
45
 TIERSKY ET AL.

concurrent psychiatric status between responders and Table 2. Performance of Responders on Psychological,
Illness-Related, and Disability Measures at Time 1 and Time 2
nonresponders at Time 1 (all p >. 05). However, the
nonresponders demonstrated lower levels of anxiety Time 1 Time 2
(responders: Mdn = 38, range = 21–78; nonresponders:
Mdn = 27, range = 20–74; p = .02) and less disability at Mdn Range Mdn Range p
Time 1 than the responders (responders: Mdn = 30, BDI 13 4–30 10 0–33 .02
range = 20–60; nonresponders: Mdn = 45; range = STAI 38 21–78 39 23–67 .66
20–70; p = .03) The median disability level of the Fatigue 60 49–63 57 17–63 .01
nonresponder group corresponded to a disability rank- CDS 30 20–60 40 20–100 .01
ing identified by the following characteristics: not con-
Note: BDI = Beck Depression Inventory; STAI = State–Trait
fined to the house, unable to perform strenuous duties, Anxiety Inventory; Fatigue = Fatigue Rating Scale; CDS = CFS
and able to perform light-duty desk work 3 to 4 hr a day Disability Scale.
but requires rest periods. In contrast, the median dis-
ability level of the responder group corresponded to a
disability ranking identified by the following character- Table 3. Performance of Responders on Neuropsychological
Measures at Time 1 and Time 2
istics: usually confined to house, unable to perform any
strenuous tasks, and able to perform desk work 2 to 3 hr Time 1 Time 2
a day but requires rest periods. Finally, there were no
significant differences between the groups in level of Mdn Range Mdn Range p
neuropsychological functioning at Time 1 (all p >. 05). CVLT–T 52 30–76 54 29–75 .89
CVLT–SDFR 11 4–16 11 3–16 .76
CVLT–LDFR 10 4–16 12 2–16 .31
Change From Time 1 to Time 2 ROCF–I 34 4–64 35 0–66 .40
ROCF–D 35 3–64 36 3–63 .47
W–DSF 9 6–14 9 5–12 .84
CFS severity and fatigue. At Time 1, all partici- W–DSB 9 3–13 7 3–12 .26
pants met both the 1988 and 1994 CDC case definition PASAT 128 60–177 137 75–189 .01
criteria for CFS, and 97% of the participants demon- MMQ 73 38–136 67 32–111 .01
strated severe CFS (see Table 1 for a definition of severe Note: CVLT = California Verbal Learning Test; CVLT–T = total
CFS). At Time 2, only 1 participant no longer met either score; CVLT–LDF = long-delay free recall; CVLT–SDF =
the 1988 or 1994 CDC criteria. Moreover, clini- short-delay free recall; PASAT = Paced Auditory Serial Addition
cian-rated CFS severity did not significantly improve Test total score; ROCF–I = Rey–Osterreith Complex Figure Test,
immediate recall; ROCF–D = delayed recall; W–DSF = Wechsler
from Time 1 to Time 2 (p = .40). Specifically, 57% of Adult Intelligence Scale–Revised Digit Span Forward–total Digits;
the CFS participants demonstrated improvement over W–DSB = Digit Span Backward–total Digits; MMQ =
time, whereas 43% did not. At follow-up, all of the par- Meta-Memory Questionnaire total score.
ticipants designated as not improved continued to dem-
onstrate severe CFS. Moreover, 45% of the improved
participants continued to rate some of their symptoms as
at least a substantial problem. Finally, although no Concurrent psychiatric status. No significant
change in CFS severity was observed, the participants change in the proportion of concurrent Axis I or Axis II
did demonstrate an improvement in level of fatigue over (all p >. 05) disorders in the sample was observed over
time (p = .01; see Table 2). time. Specifically, at both Time 1 and Time 2, 34% of
the participants met the criteria for a concurrent Axis I
Neuropsychological status. As demonstrated in disorder. In addition, no change in Axis II performance
Table 3, significant improvement from Time 1 to Time was observed with a prevalence of 45% during both
2 was noted on some of the neuropsychological vari- time periods. Despite the lack of change in the propor-
ables. Notably, a significant positive change in perfor- tion of concurrent Axis I and Axis II disorders in the
mance was observed on the PASAT, a measure of com- sample over time, a significant improvement was noted
plex information processing (p = .01) as well as on the on a measure of mood, the BDI (p = .02; see Table 2).
Meta-Memory Test, a self-report measure of attentional
and memory functioning (p = .01). No other significant Disability and employment status. As illus-
changes were found. trated in Table 2, initial level of disability significantly

46
 LONGITUDINAL ASSESSMENT IN CHRONIC FATIGUE SYNDROME

diminished at follow-up (p = .01). At Time 2, the me- Table 5. Correlations Among Fatigue, CFS Severity, Disability,
Mood, and Objective and Subjective Neuropsychological
dian level of functioning on the disability measure cor- Functioning at Time 2
responded to a disability ranking characterized by: not
confined to the house, unable to perform strenuous du- Fatigue CDS BDI Neuro MMQ
ties, able to perform light-duty desk work 3 to 4 hr a day
but requires rest periods. The sample did not change sig- Fatigue
CDS –.78*
nificantly from Time 1 to Time 2 in employment status
BDI .60* –.57*
(p >. 05). Specifically, 68% of the participants were un-
Neuro .44** –.66* .53*
employed at both time periods.
MMQ .69* –.84* .55* .59*

Note: Fatigue = Krupp Fatigue Rating Scale; CDS = CFS

Predicting Time 2 Performance From Time 1 Disability rating scale; BDI = Beck Depression Inventory; Neuro =
level of neuropsychological impairment (total number of tests
Performance failed); MMQ = Meta-Memory Questionnaire total score.
*p < .01. **p < .02.
Predicting neuropsychological performance. As
illustrated in Table 4, between-test duration was the
at baseline to contribute to lower odds of improvement
only variable that significantly predicted improvement
in disability status.
in neuropsychological functioning when the baseline
log odds were set to zero, c2(1, N = 25) = 8.16, p = .01.
Predicting employment status. Concurrent psy-
This model demonstrates that the longer the duration of
chiatric status and age at Time 1 significantly predicted
time lapsed between baseline and follow-up evalua-
employment at Time 2, when the baseline log odds were
tions, the lower the odds of improvement in
set to zero (a = 0), c2(2, N = 35) = 13.50, p = .01 (see Ta-
neuropsychological functioning.
ble 4). This model demonstrates that being older at base-
line lowers the odds of being employed at Time 2 and
that having a concurrent psychiatric diagnosis at intake
Predicting disability. Concurrent psychiatric
contributes to higher odds in favor of being employed at
history at Time 1 and age at Time 1 predicted improve-
Time 2.
ment in level of disability when the baseline log odds
were set to zero, c2(2, N = 32) = 9.63, p = .01 (see Table
4). As Table 4 illustrates, the positive coefficient for the
variable measuring psychiatric status indicates that hav- Interrelated Variables at Time 2
ing a concurrent psychiatric diagnosis at Time 1 con-
tributes to higher odds in favor of improvement in dis- The relations at Time 2 among the variables that sig-
ability. The negative coefficient for the variable nificantly changed over time were also examined. As is
measuring age reflects that there is a trend for older age illustrated in Table 5, improvement in level of fatigue,
mood, disability level, neuropsychological function-
ing, and subjective attention and memory abilities were
all interrelated.
Table 4. Logistic Regression Models for Neuropsychological
Improvement, Improvement in Disability, and Time 2 Employment
Status
Discussion
Wald
Predictors Beta SE c2(1) p
This study was designed to examine long-term
Neuropsychological change in neuropsychological functioning, psychiatric
Improvement status, disability, and employment status in individuals
Between-Test Duration –.03 0.01 6.57 .01 with CFS. Disability level, depression, fatigue, subjec-
Disability Improvement tive attention and memory, and complex information
Age –.03 0.01 3.40 .07
processing were found to improve. Moreover, when
Psychiatric Status 2.61 0.93 7.40 .01
compared to standard normative values, CFS partici-
Time 2 Employment Status
pants improved to the extent that at Time 2 they were
Age –.05 0.02 8.95 .01
Psychiatric Status 1.93 0.83 5.44 .02
functioning in the normal to near-normal range in two
of these areas. Specifically, on the PASAT, participants

47
 TIERSKY ET AL.
performed in the average range at Time 2 (Brittain, La
Marche, Reeder, Roth, & Thomas, 1991). Likewise, the
level of depression demonstrated by the sample at Time
2 fell in the mild to minimal range (Beck et al., 1961).
Thus, these findings are consistent with prior studies
(for a review, see Joyce et al., 1997).
Despite the observed improvement, the majority of
the participants continued to demonstrate CFS symp-
toms, were unemployed (68%), and remained function-
ally impaired at Time 2. Only a single individual was
found to no longer meet the 1988 or 1994 CFS criteria
at follow-up. Moreover, the median CDS score at Time
2 indicated that participants were not able to perform
strenuous duties and were only able to perform
light-duty desk work for 3 to 4 hr a day. The CDS score
indicated that even this amount of work required rest
periods. This level of disability and illness suggests a
poor overall prognosis in CFS.
It is possible that the participants in this investiga-
tion were more functionally disabled at Time 2 than
participants included in other studies. For instance, we
found higher unemployment rates in our study at Time
2 as compared to other authors (i.e., Bombardier &
Buchwald, 1995; Vercoulen et al., 1996). In addition,
Wilson et al. (1994) reported higher levels of function-
ing at follow-up in their investigation, which used the
clinician-rated Karnofsky Performance Index. They
found CFS participants to be functioning at a level be-
tween “cares for self, unable to carry on normal activity
or to do active work” and “normal activity with effort.”
This comparison between studies must be interpreted
cautiously, however, as the measures used to evaluate
outcome differed (i.e., a self-report measure of disabil-
ity was used in our investigation, and a clinician rating
of disability was utilized in the study by Wilson et al.).
This discrepancy highlights the need for a future inves-
tigation to examine long-term disability level in indi-
viduals with CFS using both self-report as well as
objective criteria, such as the Karnofsky Performance
Index.
Based on the results of this investigation, it also ap-
pears that having a concurrent psychiatric disorder at
intake (or Time 1) is positively related to long-term out-
come. Patients diagnosed with a psychiatric disorder
concurrent with their illness onset demonstrated greater
odds of improvement in level of disability than those
with no history of a concurrent psychiatric disorder.
Participants with a concurrent psychiatric diagnosis at
intake were also more likely to be employed at fol-
low-up than those without such a history.
One reason patients with a concurrent psychiatric
history may demonstrate better outcomes from CFS
48
sufferers with no such history is that the etiology of
their CFS symptoms may differ. Psychiatric disorders
such as depression have a variable course in which
symptoms fluctuate, and often a natural remission in
symptoms occurs (American Psychiatric Association,
1987). Thus, it is possible that the more favorable
course observed in participants with CFS and a psychi-
atric history reflects an underlying psychiatric etiology.
Participants with CFS with no psychiatric history, how-
ever, may have another cause for their symptoms. For
instance, it is possible that participants with CFS and no
psychiatric history have a neurologic cause to the ill-
ness, the consequence of which is a chronic and intrac-
table course. Two studies provide some support for this
notion (DeLuca, Johnson, Ellis, & Natelson, 1997;
Lange et al., 1999). Specifically, Lange et al. (1999)
found that CFS sufferers with no psychiatric history
demonstrated a greater number of MRI abnormalities
than CFS patients with a concurrent psychiatric history.
In addition, DeLuca et al. (1997) found that CFS suffer-
ers with no psychiatric history demonstrated greater
neuropsychological impairment than those with a posi-
tive psychiatric history. Future research should investi-
gate the possible differences in illness course in CFS
sufferers with differing psychiatric histories or illness
etiologies.
Moreover, the fact that some individuals with CFS
develop psychiatric disorders and others do not sug-
gests differences in coping style and adaptation. Thus,
it is also possible that the factors that maintain the ill-
ness are different in CFS participants with a psychiatric
history as compared to those with no psychiatric his-
tory. For example, participants with CFS and no psy-
chiatric history may accommodate to their illness more
readily and thus not develop an emotional disorder.
CFS patients with no concurrent psychiatric disorders
may also be more behaviorally disengaged as evi-
denced by the fact that they are more likely to be unem-
ployed than those with a psychiatric history. Illness
accommodation and behavioral disengagement have
both been found to predict poor outcome in some par-
ticipants with CFS (Ray et al., 1997). A future investi-
gation should examine changes over time in these
cognitive variables in CFS participants with differing
psychiatric histories.
In contrast to the findings of this investigation, other
authors have not found that psychiatric status at intake
predicts employment status or improvement in func-
tioning at follow-up (Bombardier & Buchwald, 1995;
Hill et al., 1999; Ray et al. 1997; Vercoulen, 1996; Wil-
son et al., 1994). These discrepant findings may be due
to methodological differences, such as the use of differ-
 LONGITUDINAL ASSESSMENT IN CHRONIC FATIGUE SYNDROME
ent outcome measures or the use of different measures
to evaluate psychiatric distress. For example,
Vercoulen et al. (1996) and Wilson et al. (1994) used
self-reported change as a final outcome variable. Other
primary outcomes have included self-reported fatigue
and functional impairment (Ray et al., 1997; Vercoulen
et al., 1996); clinician-rated functional impairment
(Wilson et al., 1994); change in immunological param-
eters (Wilson et al., 1994); clinician-rated improve-
ment (Hill et al., 1999); and return to work (Bombardier
& Buchwald, 1995). Measures of psychiatric status at
baseline have included a variety of measures such as
the Hospital Anxiety and Depression Scale (Ray et al.,
1997), the neuroticism subtest of the Eysenck Personal-
ity Inventory, and the Diagnostic Interview Schedule
for the DSM–III–R (American Psychiatric Association,
1987; Bombardier & Buchwald, 1995; Hill et al.,
1999). Thus, due to the use of differing measures, it is
difficult to directly compare the studies.
Demographic factors also appear to be related to
long-term outcome. In this study it was found that older
patients at intake had a higher risk of unemployment at
Time 2, a finding that has been observed by other au-
thors (for a review, see Joyce et al., 1997). There was
also a trend for older patients to have lower odds of im-
provement on the disability measure.
One limitation of our investigation is that the dura-
tion between baseline and follow-up testing was not
constant for all participants. This limitation was ad-
dressed by including between-test duration as a vari-
able in the regression analyses. This allowed us to
examine how elapsed time may have affected our three
main outcomes: neuropsychological impairment, dis-
ability, and employment. We found that between-test
duration only impacted neuropsychological function-
ing. Specifically, the longer the duration between base-
line and follow-up testing, the lower the odds of
detecting improvement. Given this finding, it is possi-
ble that our repeated measures analyses did not capture
significant changes on some of the neuropsychological
measures.
Finally, the findings of our investigation have two
main clinical implications. Given that participants
demonstrate some improvement in neuropsychological
functioning, periodic reevaluation appears warranted
so that level of functioning can be most accurately esti-
mated. Reevaluation can also provide information
about whether interventions such as psychotherapy or
vocational rehabilitation are indicated. In addition, as is
consistent with the findings of other authors, we noted
that many areas of functioning improved concurrently
(Ray et al., 1997). These related improvements suggest
that treatment targeted toward improving one or a few
of the areas may result in improvement in the other do-
mains. For instance, cognitive behavioral therapy
(CBT), which has been found to improve overall level
of disability and mood in CFS patients (Deale, Chalder,
Marks, & Wessely, 1997; Sharpe et al., 1996), may also
result in an improvement in level of
neuropsychological impairment. A topic for future re-
search is whether CBT can improve cognitive function-
ing in CFS.
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Original submission November 15, 1999
Accepted June 19, 2000
Appendix
Management of Missing Values
When creating the impairment index, the following
methods were used to statistically manage missing val-
ues. The test variable PASAT total score had nine miss-
ing observations at Time 1 because the participants
were not administered the measure. Values for these
nine missing data points were computed using an opti-
mal regression model that included the remaining
seven cognitive measures (i.e., CVLT–T, CVLT–LDF,
CVLT–SDF, ROCF–I, ROCF–D, WAIS–R Digit Span
Forward and Digit Span Backward subtests). Spe-
cifically, to generate the scores for the nine missing val-
ues, all seven of the cognitive variables were entered in
the multiple linear regression model, and a stepwise
backward elimination procedure was performed. The
final model, which was selected on the basis of having
the smallest sum of square error (SSE), included the fol-
lowing predictor variables: ROCF–I, CVLT–SDF, and
ROCF–D (SSE = 25.55). An analysis of variance
showed that this regression model was significant with
p = .00. Although the model coefficients corresponding
to ROCF–I and CVL–SDF were not significant (p = .21
and .22, respectively), they were kept in the final model
because the objective of getting the model with the
smallest SSE, which yields the best prediction, was met
with their inclusion. Thus, the final model used to pre-
dict PASAT total score for the nine missing vales was
the following: PASAT (score) = 76.68 + 1.67 ×
ROCF–D (score) + 1.90 × CVL–SDF (score) – .96 ×
ROCF–I (score).