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Smith.

Review Article
WORLD JOURNAL OF PHARMACEUTICAL
World Journal of Pharmaceutical and Medical Research
ISSN
2455-3301
AND MEDICAL RESEARCH

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CHRONIC FATIGUE SYNDROME, DEPRESSION, SLEEP, AGE, INTELLIGENCE AND
MEMORY
Andrew P. Smith*
PhD, School of Psychology, Cardiff University.
*Corresponding Author: Prof. Andrew P. Smith
PhD, School of Psychology, Cardiff University.

Article Received on 15/05/2022

Article Revised on 05/06/2022

Article Accepted on 26/06/2022

ABSTRACT
Background: Memory problems are frequently reported by Chronic Fatigue Syndrome (CFS) patients. These selfreports are often not confirmed using objective memory tests. Indeed, conflicting results have been obtained inprevious studies examining the performance of CFS patients on a variety of memory tasks. Results have shownthat CFS patients perform working and semantic memory more slowly but show no decrease in accuracy. The
present study examined whether sleep disturbances, depression, age and intelligence may modify the effects of
CFS on memory. Methods: CFS patients were recruited from a specialist clinic and compared with healthy
controls. Three experiments were carried out. The first used memory tasks designed to examine the different
components of working memory. The second used working memory and semantic memory tasks and also
examined psychomotor speed. The third used the "Doors and People" task, which measures immediate recall andforgetting of names and visual shapes. Measures of intelligence, insomnia and depression were also recorded.
Results: The CFS patients reported frequent memory problems and showed a trend of impaired memory
performance. However, only the differences in speed scores and the recall of shapes were significant. Depression,
insomnia, age and intelligence did not significantly modify the performance of the CFS patients. Conclusions:
CFS patients reported frequent memory problems, but objective testing largely failed to confirm this. The CFS
patients were slower at several tasks (Digit-Symbol Substitution; Semantic Processing; writing and simple reactiontime), and this slowing may be involved in the poorer immediate recall of shapes. Depression, insomnia, age andintelligence did not change the CFS effects. Future research should use large sample sizes as the effect sizes ofbeing in the CFS group were small.
KEYWORDS: Chronic Fatigue Syndrome; Depression; Sleep problems; Intelligence; Age; Memory; Working
memory; Semantic Memory; Writing Speed; Simple reaction time; Doors and People Test.
patients.[17] Visual memory tasks are also moresensitive.[1]Research has also examined the type of processing that
may be involved. These memory impairments have beeninterpreted in terms of changes in the amount of effort
applied or slower information processing.[12, 23] One
study suggested that impairments reflected poorer initialstorage rather than retrieval. [19] Results from a recent
study[31] suggest that slower responding may account for
impairments in episodic, semantic and working memorytasks. This explanation can also account for slower
responses by CFS patients in focused attention andcategoric search tasks.[32]INTRODUCTION
Persistent debilitating fatigue is the primary symptom ofChronic Fatigue Syndrome (CFS). Cognitive problems
such as reports of impairment of memory and loss ofconcentration may be reported by a large percentage (6675%) of patients. This has led to a number of studies
using objective tasks to measure possible memory
impairments in CFS.[1-30] Initial findings showed that the
memory problems reported by the patients are notreplicated with objective measurement.[4,21] Indeed, anumber of studies have failed to find significant memory
differences between CFS patients and healthy
controls.[2,3,5,7,13,14,20,22,24,29] In contrast, some research has
demonstrated
memoryimpairments
inCFS
patients.[9,10,11,12,18,19,23, 25,26,27,28,30] Research has also
found that only certain types of memory tasks are
impaired in CFS patients. For example, more demanding
memory tasks are more likely to be impaired in CFS

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Other research has combined memory tasks with brain
scanning, and the results showed that CFS patientsprocess challenging auditory information as accurately as
controls but have to use more regions of the network
associated with the verbal WM system. Individuals with
CFS appear to have to exert greater effort to process│

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World Journal of Pharmaceutical and Medical Research

auditory information as effectively as demographicallysimilar healthy adults.[28]Study 1: Working memory
Participants
CFS patients: 8 males (mean age: 48.7 years, range 3659 years), 13 females (mean age: 39.3 years, range 1856). 61.9% married, 14.3% single, 23.8% divorced or
separated.

It has been suggested that CFS may have many
similarities to depression. This has led to studies
comparing CFS and depressed patients with healthy
controls.[6,8,15,30] An alternative way of examining the roleof depression in memory problems in CFS is to compare
CFS patients with and without depression. Effects of
CFS may be restricted to those with or without
depression. Alternatively, depression may influence
memory, and the removal of this influence from the error
term makes it more likely that you can detect an effect of
CFS.

Controls: 8 males (mean age: 39.9, range 18-57), 12
females (mean age 45.5 years, range 34-61 years). 35%
married, 35% single, 30% divorced or separated.
The CFS and control groups did not differ in terms ofage or socio-economic status.
The symptoms reported by the CFS patients are shown in
Table 1. The CFS patients had a mean illness duration of
110.3 months (range 24-360 months). 57.1% were in thehigh depression (based on a median split) and highinsomnia groups.

Another factor influencing the performance of CFS
patients may be sleep disturbance. This is common inthis group and is also known to have an effect on their
cognitive functioning.[33] Again, it may be the CFS groupwith disrupted sleep that shows the greater performancedecrement. Alternatively, removing the influence ofsleep disturbance from the error term may make it easier
to detect effects due to CFS. There are also otherbackground factors that need to be controlled in researchon memory. Memory performance will change with age
and intelligence. It has not been suggested that subgroups of CFS patients based on age or intelligence show
the greatest impairments. However, both age andintelligence have direct effects on memory, and theseeffects should be removed in order to obtain a clearer
profile of the effects of CFS on memory.

Table 1: Chronic Fatigue Syndrome Sample:
Symptom checklist.
Physical weakness(50% more than before you were ill)
Excessive fatigue(50% more than before you were ill)
Legs feeling heavy
Muscle pain
Painful joints
Pain in chest
NauseaIndigestion
Bloated stomach
Wind
Sore Throat
Headache
EaracheSore eyes
Sensitive to noise
Sensitive to light
Feeling hot/cold
Sweating
Shivering
Swollen glands
Racing heart
Insomnia
Depression
Anxiety/Panic
Loss of concentration
Loss of memory
Allergies

The aim of the present study was to continue the researchon memory in CFS patients. The first aim was to confirm
that these patients report real-life memory problems.
Secondly, a range of different memory tasks was used inorder to identify sensitive outcomes. It was predicted thatthe speed measures would be more sensitive than theaccuracy variables. Memory for shapes was also
examined, and it was predicted that this visual memory
might be impaired in CFS. Finally, the analyses included
measures of sleep disruption, depression, age andintelligence. Both the direct effects of these factors andtheir interactions with CFS/control groups were
examined.
MATERIALS AND METHODS
Three separate studies were carried out. These studies
were carried out with the informed consent of thevolunteers and the approval of the local regional ethicalcommittee. The present article presents studies thatexamined CFS and memory, then looked at depression,
sleep, age and intelligence. Depression was measured
using the Beck Depression Index,[34] insomnia from thesymptom checklist, and intelligence was based on
National Adult Reading scores (NART).[35]

85.0%
81.0%
81.0%
76.2%
61.9%
42.9%
52.4%
38.1%
57.1%
52.4%
52.4%
57.1%
23.8%
33.3%
52.5%
66.7%
61.7%
57.1%
41.7%
38.1%
42.9%
57.1%
57.1%
57.1%
81.0%
76.2%
28.6%

Working Memory Tests
These tasks were designed to investigate components ofworking memory (the central executive, articulatory loop
and the visuospatial scratchpad).[39]

The CFS patients were recruited from a specialist clinic.
The healthy controls were recruited from a participant
panel.

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World Journal of Pharmaceutical and Medical Researcha) Serial Recall Test
This task is designed to investigate the articulatory loopof Baddeley's working memory model. A sequence ofeight single-digit numbers was displayed on thecomputer screen. The numbers were presented
consecutively at a rate of one per second. Afterobserving the sequence, participants were required towrite down the numbers in the order in which they had
been shown. If they were unsure of a number, they wereencouraged to guess. This process was repeated fivetimes, and their responses were recorded on a response
sheet.

index of physicalsymptoms
Cognitive failuresquestionnaire
Perceived stress

Analyses of variance were carried out on theperformance data. The first compared the patients andthe controls, whilst the second subdivided the patientsand controls and also included age as a factor (groups
being divided by a median split). Degrees of freedom
vary because of missing data. There was no statisticallysignificant difference in mean scores of the CFS andcontrol groups on the serial memory task (F=2.55,
df=1,40, p < 0.1). The analysis of variance for runningmemory demonstrated no significant effect on the group,
indicating that there were no significant differences inmean performance (F=2.75, df=1,40, p <0.1). The
analysis of variance for the visual memory sequence also
revealed no significant difference in the performance of
CFS patients and healthy controls (F=1.14, df=1,34,
P<0.29).
The addition of age as a factor did not modify thedifferences between CFS and control groups. A third
analysis included intelligence as a factor. Again division
was based on a median split. This revealed an effect ofintelligence on serial and visual memory sequence tasks(F==5.46, df-=1,35, P<.05; F=7.68, df-=:1,29, P<.01),
although no effect was found for running memory.
Again, these analyses showed no significant differences
between the CFS/control groups.

Table 2: Mental and physical symptoms of C FS
patients and controls (means, SDS in parentheses).

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50.6 (14.7)

26.9 (13.8)

15.1(6.5)

7:8 (9.8)

49.5 (10.4)
25.9 (8.0)

36.3 {10.0)
6.4 (7.9)

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22.7 (7.4)

The performance of the CFS patients was generally
worse than the controls: Serial recall: CFS mean: 60.8% correct; Controls:
69.9% correct.
 Running memory: CFS mean 51.0% Controls:61.2%
 Visual memory: Patients: 42.2% Controls: 45.4%

Psychosocial Questionnaires
Psychosocial questionnaires showed that patients had alower positive mood[36], higher negative mood[36], higher
anxiety[37] and depression[33], greater fatigue[38], moresomatic symptoms[38] and more cognitive difficulties[38](see Table 2).

Controls
36.6 (11.1)
14.2 (11.1)
30.7 (6.8)
25.4 (11.5)
29.9 {20.1)

27.4 (10.2)

RESULTSc) Spatial Memory Task
This task is designed to investigate the visuo-spatial
scratch pad described in Baddeley's working memory
model. Participants were asked to concentrate on five red
buttons displayed on a response box. The red buttons lit
up in a randomised sequence consisting of eight flashes.
After observing the light sequence, they were required toreproduce the sequence by pressing the buttons in thesame order as previously presented. This process was
repeated five times, and their responses were recorded on
the computer.

CFS Patients
28.3 (11.8)
24.1(10.5)
43.3 {9.6)
59.5 (17.1)
64.2 (12.0)

45.0 (13.1}

Intelligence
National Adult Reading Test (NART)
A test of reading ability, well-preserved in those withcognitive impairment, involves reading out loud 50
words differing in pronounceability. Scores give an
estimate of premorbid IQ.

b) Running Memory Task
Similar to the serial recall task, this was designed to
examine the central executive of Baddeley's working
memory model. A sequence of consecutive single-digit
numbers was presented at a rate of one per second.
However, the length of the sequence is unknown, andthus they did not know when it would end. Participants
were required to write down the last five digits of thesequence in the order in which they had been presented.
If unsure of a number, they were again encouraged toguess. This process was repeated three times, thesequence length varying each time.

MeasurePositive mood
Negative mood
CESD depression
Somatic symptoms
FatigueCognitive
difficulties
Beck depression
inventory
Trait anxiety
Cohen-Hobermann

61.2 (17.8)

Further sets of analyses were carried out, splitting thegroups into those with high and low levels of depression(on the basis of a BDI median split; CFS depressed:
47.2%, CFS not depressed: 65.0%; Control depressed:
42.5% Control not depressed: 66.6%). The analyses
demonstrated a significant effect of depression on
running memory (F=9.22, df=l,36, p<0.01), but it was
not found to be related to performance on either serial
recall or visual memory sequence. In addition, CFS
participants were also sub-divided into those with and│ISO 9001:2015 Certified Journal│52

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World Journal of Pharmaceutical and Medical Researchwithout insomnia. Analyses showed no statisticalsignificance of sleep on performance for any task:
 Running memory F=2.54, df=2,36, p=0.09,
 Serial recall F=2.42, df=2,37, p=0.10,
 Visual memory F= 0.78, df=2,31, p=0.47.

Sensitive to light
Feeling hot/cold
Sweating
Shivering
Swollen glands
Racing heart
Insomnia
Depression
Anxiety/Panic
Loss of concentration
Loss of memory
Allergies

Summary of results from study 1
Over 75% of the CFS patients reported memory
problems. Performance of objective tests measuring thecomponents of working memory showed that the CFS
patients were worse than the controls but that the effects
were not statistically significant. This suggests that larger
sample sizes are needed to detect such objective memory
impairments. Inclusion of age, intelligence, depression
and insomnia did not alter the significance of thedifference between patients and controls.

Table 4: Mental and physical symptoms of CFS
patients and controls (means, SDS in parentheses).
MeasurePositive mood
Negative moodSomatic symptoms
FatigueCognitive difficulties
Beck depression
inventory
Trait anxiety
Cohen-Hobermann
index of physicalsymptoms
Cognitive failuresquestionnaire
Perceived stress

Study 2: Working memory, semantic processing andmotor speed.
The next study examined both working memory andsemantic memory tasks and included measures of bothspeed and accuracy. Motor speed was also measured
using writing and simple reaction time tasks.
Participants
24 CFS patients aged 21 to 65 years took part in the
study. The mean and standard deviation of their ages
were 43.8 and 10.6 years. Fifteen (62.5%) were female,and nine (32.5%) were male. The average length of thepatients' illness was 97.2 months, with a range of 1.5 - 30
years.
The 19 healthy controls were matched for age, gender,and educational level of the CFS patients. The mean and
SD of their ages were 44.7 and 13.7 years. There were 11
females and eight males.

Table 3: Chronic Fatigue Syndrome Sample:
Symptom checklist.

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CFS Patients
27.7 (10.2)
22.5 (12.0)
54.4 (18.2)
59.4 (13.7)
46.5 (14.7)

Controls
35.8 (11.9)
14.5 (11.0)
25.4 (15.0)
24.2 (20.1)
22.8 (11.7)

14.7 (7.3)
48.3 (11.5)
23.5 (7.8)

8.1 (8.1)
33.4 (11.1)
5.7 (6.1)

58.7 (14.0)

41.4 (16.9)

25.2 (8.9)

23.6 (10.1)

DESCRIPTION OF THE TESTS
Semantic Processing Test
This was a timed test of semantic memory and involved
answering true (e.g. canaries have wings) or false (e.g.
dogs have wings) to fifty simple sentences indicating
their general knowledge. Speed and accuracy wererecorded.

The reported symptoms and psychosocial scores areshown in Tables 3 and 4.

Physical weakness(50% more than before you were ill)
Excessive fatigue(50% more than before you were ill)
Legs feeling heavy
Muscle pain
Painful joints
Pain in chest
NauseaIndigestion
Bloated stomach
Wind
Sore Throat
Headache
EaracheSore eyes
Sensitive to noise

66.7%
70.8%
58.3%
50.0%
54.2%
54.2%
41.7%
29.2%
50.0%
79.2%
75.0%
37.5%

Recall of Category Instances
The participant wrote down as many instances from agiven category (e.g. animals or colours) as they could ina minute.

87.5%
83.3%

Digit-Symbol Substitution Test
This is a test of search and memory, measuring working
memory. Participants drew symbols correctly matching
digits which had been paired in a table at the top of the
sheet. They carried out this task for 3 minutes, and speed
and accuracy were recorded.

75%
83.3%
79.2%
45.8%
29.2%
41.7%
58.3%
45.8%
58.3%
66.7%
33.3%
58.3%
54.2%

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PSYCHOMOTOR TESTS
Word writing
This writing test measured the speed with which theparticipants copied a list of 25 5-letter words.
Simple reaction time test
This test of psychomotor speed measured the mean
reaction time for responses to the appearance of a solid│

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World Journal of Pharmaceutical and Medical Researchsquare in a box on the screen. This test was completed inthree minutes.

Simple Reation time (msecs; mean (sd))
 CFS/high depression: 404 (94)
 CFS/low depression: 367 (149)
 Controls/high depression: 388 (178)
 Controls/low depression: 321 (88)

RESULTSThe CFS patients showed a general trend for worse
performance, but the majority of the effects were notsignificant (see Table 5). The writing speed of patientswith CFS was significantly slower F=5.37, df=1,41,
p<.05.

When the CFS group were subdivided into those withand without insomnia, the main effects of groups werealso observed in the psychomotor tasks and semantic
processing speed. These significant effects reflected the
CFS/insomnia group being slower than the CFS/no
insomnia group and controls.

Age and intelligence as covariates:
The age and NART scores were employed as covariates,
CFS/controls group was the independent variables, andthe performance scores (number of instances recalled,
the speed and accuracy of semantic processing, andnumber of symbols drawn and accuracy on DSST) wereused as dependent variables. The results showed effects
of age on tests of recall of instances, semantic processing
speed, speed on DSST (number of symbols drawn),
writing speed, and simple reaction time. This shows thatthe tests are sensitive measures of changes in the state
due to ageing. The NART scores only significantly
affected semantic processing speed only (p<.01). Afterage and intelligence were adjusted, a significant
difference between patients with CFS and matched
controls was still only found for writing speed.

Semantic processing speed (secs; mean (sd))
 CFS/insomnia
140 (24)
 CFS/no insomnia
109 (34)
 Controls
104 (34)
Writing speed (secs; mean (sd))
 CFS/insomnia
55.6 (17) CFS/no insomnia
53.4 (19) Controls
43.7 (10)Simple reaction time (msecs)
 CFS/insomnia
457 (160)
 CFS/no insomnia
348 (68)
 Controls
332 (110)

Table 5: Performance of CFS and control groups on
the memory and psychomotor tasks (scores are themeans, SDS in parentheses).
Test
NART
Recall of category instances
Semantic processing speed- completion time secs.
Semantic processing acc %Digit symbol – speed –number completed
Writing speed - secs
Simple Reaction Time msecs

CFS
35.0
(7.2)
14.0
(4.5)
122.1
(33.1)
96.8
(2.5)
72.8
(19.8)
54.3
(7.5)
388
(120)

Controls
38.8
(5.1)
15.6
(4.2)
104.2
(33.7)
97.5
(2.3)
81.1
(23.3)
43.7
(9.7)
332
(110)

Summary of Study 2This study confirmed that CFS patients report problems
with memory. It also confirmed the slower motor
performance of CFS patients, both in terms of simple
reaction time and writing speed. The semantic memory
and working memory tasks were also performed more
slowly by the CFS group, but their accuracy was similar
to the controls. Effects of age, intelligence anddepression were found, but the addition of these factors
did not change the CFS effects. The motor tasks were
performed more slowly by the CFS patients withinsomnia, and those without insomnia showed little
difference from the control group. The memory tasks
were not influenced by insomnia.
The next study used a task which involved real-life
memory tasks, including a task often reported asproblematic by CFS patients, namely recall of people's
names.

Effects of depression
The CFS patients and controls were sub-divided into twogroups based on their median BDI scores to assess theeffects of depression in CFS. The results showed thathigh depression was associated with slower motor
responses, but it had no effect on the memory tasks anddid not change the difference between the CFS patientsand controls:

Study 3: Doors and people task
This study used the Doors and people task[40], whichmeasures immediate and delayed recall of verbal andvisual material.
Participants
The demographic characteristics of the participants are
summarised below:

Writing speed (secs; mean (sd))
 CFS/high depression: 55.1 (19.2)
 CFS/low depression: 53.3 (15.7)
 Controls/high depression: 46.3 (11.6)

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Controls/low depression: 43.8 (9.7)│

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Somatic symptoms
FatigueCognitive
difficulties
Beck depression
inventory
Trait anxiety
Cohen-Hobermann
index of physicalsymptoms
Cognitive failuresquestionnaire
Perceived stress

Mean age of female CFS patients (N=16): 45.3
years, range 22-65 years
Mean age of male CFS patients (N=8): 41.8 years,
range 24-59 years
Mean age of female controls (N=11): 401. Years
range 22-65 years
Mean age of male controls (N=7): 49.1 years, range
28-67 years.
Mean illness duration CFS patients: 95.2 months

The results from the symptom checklist are shown in
Table 6.
Table 6: Chronic
Symptom checklist.

Fatigue

Syndrome

Physical weakness(50% more than before you were ill)
Excessive fatigue(50% more than before you were ill)
Legs feeling heavy
Muscle pain
Painful joints
Pain in chest
NauseaIndigestion
Bloated stomach
Wind
Sore Throat
Headache
EaracheSore eyes
Sensitive to noise
Sensitive to light
Feeling hot/cold
Sweating
Shivering
Swollen glands
Racing heart
Insomnia
Depression
Anxiety/Panic
Loss of concentration
Loss of memory
Allergies

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14.7 (7.3)

10.0 (7.0.1)

45.5 (10.7)
25.0 (8.0)

40.5 (11.8)
7.5 (6.1)

56.0 (19.4)

38.8 (16.4)

23.6 (8.9)

22.6 (11.5)

Performance Tasks
Two tasks were used, the Doors and People test and asimple reaction time task. Immediate recall was
examined, followed by the simple reaction time task, andthen delayed recall.

87.5%
87.5%
79.2%
83.3%
79.2%
20.8%
50.3%
20.8%
50.0%
33.3%
50.0%
79.2%
29.2%
58.3%
70.8%
58.3%
75.0%
58.3%
41.7%
41.7%
25.0%
41.7%
41.7%
45.8%
95.8%
87.5%
37.5%

The Doors and People Test
Immediate and delayed visual and verbal recall tasks
were taken from the 'Doors and People' memory test.
This test was thought to provide better ecologicalvalidity for investigating the more subtle memory
impairments noted by CFS patients in their everyday
lives. Both the People and Shapes tests used in the study
were contained in a single flip chart presented toparticipants. For the Shapes test, participants were
provided with a pencil and paper. Scoring details andconversion tables were taken from the Doors and People
testing manual.
Immediate verbal recall
The 'People' test was comprised of four photographspresented via a flip chart. A name and occupationaccompanied each photograph. Participants were asked
to learn the 'names' of the four people and theiroccupations. Each photograph was presented for threeseconds. After all, had been presented, the recall was
prompted by the researcher with the occupation of each
person, e.g. "What was the doctor's name?" Participants'
performance was then scored. If the names were recalled
correctly on trial one, then participants proceeded with
the Shapes test; if not, the procedure was repeated fortrials two and three.
Immediate visual recall
The 'Shapes' test contained four simple drawings basedon a 'cross' design. Participants were asked to look at
each drawing for five seconds and then copy it onto thepaper provided. When all four had been copied, theresearcher removed the copy and asked participants todraw them again from memory. If the drawings were notcompletely recalled correctly, then participants wereshown the drawings again. This time they were notallowed to copy them, and the presentation time was
reduced to three seconds. This procedure was followed
for trials two and three.

Table 7: Mental and physical symptoms of CFS
patients and controls (means, SDS in parentheses).
CFS Patients
28.6 (10.5)
21.3 (10.5)

23.6 (11.7)
27.7 (15.3)
25.6 (13.0)

Sample:The patients and controls also completed psychosocial
questionnaires, and the usual differences between thegroups were found (a more negative mood; greater
fatigue; more cognitive difficulties; more somatic
symptoms; higher anxiety and depression). These areshown in Table 7.

MeasurePositive mood
Negative mood54.3 (19.8)
64.6 (19.6)
45.0 (16.5)

Controls
34.8 (10.8)
15.8 (10.5)

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World Journal of Pharmaceutical and Medical Researchgroup SRT was only significant at the one-tailed level (F= 3.80, df=1,37, p<0.1 and p>0.05).

Delayed verbal and visual recall elements of bothtasks
For the People test, participants were asked to recall thenames they had learned earlier. Their recall was recorded
as the number correct. Participants were then asked toreproduce the drawings from the Shapes task. For
analysis, participants' raw scores were converted into
age-scaled scores using age-group norm tables listed in
the Doors and People test.

Intelligence was found to have a highly significant effectfor age-scaled people (F = 14.21, df=1,39, p<0.01),
shapes (F = 14.13, df=1,39, p<0.01) and combined agescaled recall (F= 9.52, df=1,39, p<0.01). This did notalter the significant differences between CFS patientsand controls found for shapes nor the non-significant
differences found for both people and combined recall.
There were no significant effects of intelligence on either
verbal (people), visual (shapes) or overall (verbal andvisual) forgetting scores (p>0.1). Thus, immediate recall
was found to be sensitive to variations in premorbid
intelligence, whilst forgetting scores were not. Scores
used in the analysis were adjusted for age-group norms,
and so age was not introduced as a covariate.

Simple Reaction Time task:
This was the same task as described in study 2.
RESULTS
Simple reaction time task
As has been found in previous research, the patient groupwere significantly slower at the SRT task compared withthe control group performance (F = 4.97; df=1,40,
p<0.05). The mean reaction time for patients was 363.5(ms) compared with a mean of 297.1 (ms) for the control
group.

The role of depression in the performance of memory
and SRT tasks
After both groups were sub-divided into high (scoring
above the median, 10.5) and low (below 10.5)
depression, a two-way ANOVA showed a highly
significant effect of depression on the combined agescaled recall (F =5.05, df=1,36, p<0.05). Age-scaled
people did not quite reach significance at the 5% level (F= 4.01, df=1,36, p>0.05). No significant effects of thedepression were found for either SRT, age-scaled shapes(p>0.1), verbal forgetting (p>0.05), or visual and overall
forgetting tasks (p>0.1).

The results for the two groups on the different memorytasks are shown in Table 8.
Table 8: Performance of CFS patients and controlson the memory tasks (scores are the means and SDS
and are age-adjusted).
CFS(N=24)
10.4 (3.5)
10.25 (3.2)
10.6
(3.5)
9.2
(3.4)
10.5
(2.4)
9.8
(3.55)

Age-scaled People
Age-scaled shapes
Combined agescaled recall
Verbal forgetting
Visual forgetting
Combinedforgetting

Controls(N=18)
11.5 (2.7)
12.61 (2.85)
11.5
(3.0)
9.7
(3.2)
10.1
(2.6)
9.8
(3.0)

Effects of insomnia
Patients were divided into those with and without
insomnia and compared with control group performanceusing analysis of variance. There was a slight effect of
sleep on SRT performance, showing patients withinsomnia to be slower than other patients, though this did
not quite reach significance at the 5% level (F = 2.81,
df=2,39 p<0.1). The effects of sleep on memory
performance were also analysed for age-scaled memory
scores. No significant differences were found for agescaled people, combined recall, verbal and visual
forgetting and overall forgetting scores (p>0.1). The
significant effect of groups on age-scaled shapes scores(F = 48.96, df=2,39 p<0.01), was found by post-hoc
testing to reflect only a difference between patientgroups and controls, as the control group was not divided
by insomnia.

Comparison of patient and control· group performance ofimmediate verbal and visual recall and forgetting, takenfrom the difference between immediate and delayedrecall found only age-scaled 'shapes' performance to besignificantly different between the two groups (p < 0.1).
No significant differences were found for age-scaled'people' (F = 1.28, df=1,40, p>0.1), combined age-scaled
recall, visual and verbal tests (F = 0.72, df=1,40, p>0.1),
age-scaled 'verbal forgetting', people scores (F = 0.20,
df=1,40, p>0.1), age- scaled 'visual forgetting', shapes
scores (F = 0.20, df=1,40, p>0.1) and 'overall forgetting'combined verbal and visual age-scaled forgetting(F = 0.00, df=1,40, p>0.1).

Summary of study 3
These results confirm the subjective reports of memory
problems by CFS patients. They also confirm the slower
reaction times of the CFS patients. The only memorytask which showed a significant difference between the
CFS and control groups was the immediate recall of
shapes. These significant effects were not due tointelligence, depression or insomnia. No other significant
effects of CFS were observed when other factors were
included in the analyses, although these other variables

The effect of age and intelligence on the performanceof memory and SRT tasks
After controlling for the possible effects of age andintelligence, the difference between patient and control

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World Journal of Pharmaceutical and Medical Research

did have direct effects (e.g., intelligence was important in
immediate recall but not forgetting).

impairment in myalgic encephalomyelitis/chronic
fatigue syndrome (ME/CFS). Sci Rep., Feb 9, 2022;12(1): 2157. doi: 10.1038/s41598-021-04764-w.
2. Busichio K, Tiersky LA, Deluca J, Natelson BH.
Neuropsychological deficits in patients with chronic
fatigue syndrome. J Int Neuropsychol Soc., Mar,2004;
10(2):
278-85.
doi:
10.1017/S1355617704102178.
3. Caseras, X., Mataix-Cols, D., Giampietro, V.,
Rimes, K. A., Brammer, M., Zelaya, F., Chalder, T.,
Godfrey, E. L. Probing the working memory systemin chronic fatigue syndrome: A functional magnetic
resonance imaging study using the n-back task.
Psychosomatic Medicine, 2006; 68(6): 947-955.
https://doi.org/10.1097/01.psy.0000242770.50979.5f
4. Cockshell SJ, Mathias JL. Cognitive functioning inpeople with chronic fatigue syndrome: a comparison
between subjective and objective measures.
Neuropsychology, May, 2014; 28(3): 394-405. doi:
10.1037/neu0000025.
5. Cockshell SJ, Mathias JL. Cognitive deficits inchronic fatigue syndrome and their relationship to
psychological status, symptomatology, and everyday
functioning. Neuropsychology, Mar, 2013; 27(2):230-42. doi: 10.1037/a0032084.
6. Constant EL, Adam S, Gillain B, Lambert M,
Masquelier E, Seron X. Cognitive deficits in patientswith chronic fatigue syndrome compared to thosewith major depressive disorder and healthy controls.
Clin Neurol Neurosurg, May, 2011; 113(4): 295302. doi: 10.1016/j.clineuro.2010.12.002.
7. Cope H, Pernet A, Kendall B, David, A. Cognitive
functioning and magnetic resonance imaging inchronic fatigue. British Journal of Psychiatry, 1995;
167: 593–597.
8. DeLuca J, Johnson SK, Beldowicz D, Natelson BH.
Neuropsychological impairments in chronic fatigue
syndrome, multiple sclerosis, and depression. J
Neurol Neurosurg Psychiatry, Jan, 1995; 58(1) :3843. doi: 10.1136/jnnp.58.1.38.
9. Deluca J, Christodoulou C, Diamond BJ, Rosenstein
ED, Kramer N, Natelson BH. Working memory
deficits in chronic fatigue syndrome: differentiating
between speed and accuracy of information
processing. J Int Neuropsychol Soc., Jan, 2004;
10(1): 101-9.
doi: 10.1017/S1355617704101124.
10. Dobbs BM, Dobbs AR, Kiss I. Working memory
deficits associated with chronic fatigue syndrome. J
Int Neuropsychol Soc., Mar, 2001; 7(3): 285-93.
doi: 10.1017/s1355617701733024.
11. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins
JG, Komaroff A. The chronic fatigue syndrome: acomprehensive approach to its definition and study.
International Chronic Fatigue Syndrome Study
Group. Ann Intern Med., Dec 15, 1994; 121(12):953-9. doi: 10.7326/0003-4819-121-12-19941215000009.
12. Grafman J, Schwartz V, Dale JK, Scheffers M,
HouserC,
StrausSE.
Analysisof

DISCUSSION
The results presented here confirm subjective reports ofmemory problems by CFS patients. They also confirm
slower reaction times and demonstrate that the writing
speed of CFS patients is slower. The speed of responseby CFS patients in certain semantic memory andworking memory tasks was also slower, althoughaccuracy was not impaired. All of these results confirm
the view that response speed may underlie many of thereported memory impairments of CFS patients. Thisview was supported by the results from the Doors andPeople test, where the shapes test, requiring a motor
response, was the only task that showed impaired
performance by the CFS group.
Analyses including age, intelligence, depression andinsomnia provided little evidence of the effects of CFS
reflecting these factors. This does not mean that thesevariables have no effects on performance, but rather,
they are direct effects rather than modifications of theeffects of CFS. These effects of age, intelligence,
depression and insomnia demonstrate the sensitivity ofthe tests, which shows that the limited effects of CFS do
not reflect the use of insensitive measures.
One important factor to consider is the size of the effectsof CFS. In all of the studies, the general trend of theresults was for the CFS group to be impaired relative tocontrols. The lack of significance probably reflects theeffect size. Future research on memory impairments in
CFS should be powered to detect small effect sizes rather
than the moderate sizes that much of the previous
research has tried to detect.
CONCLUSIONS
The results of the present studies confirm that CFS
patients report memory impairments. Objective testing of
memory showed few significant differences between
CFS patients and controls, although the general trend
was for the CFS group to have worse performance thanthe controls. Significant effects were found in the speedof performance, and this was observed in reaction times,
writing speed and the speed of certain memory tasks.
The immediate visual recall involving drawing shapes
was also significantly worse in the CFS group. Age,
intelligence, depression and insomnia had some direct
effects of performance but did not underlie effects of
CFS. Future research should consider the effects of CFS
on memory as small effects and use appropriate sample
sizes to obtain statistically significant differences fromcontrols.
REFERENCES
1.

Aoun Sebaiti M, Hainselin M, Gounden Y, Sirbu
CA, Sekulic S, Lorusso L, Nacul L, Authier FJ.
Systematic review and meta-analysis of cognitivewww.wjpmr.com│

Vol 8, Issue 7, 2022.

│

ISO 9001:2015 Certified Journal│

57

Smith.

World Journal of Pharmaceutical and Medical Researchneuropsychological functioning in patients withchronic fatigue syndrome. J Neurol Neurosurg
Psychiatry, Jun, 1993; 56(6): 684-9. doi:
10.1136/jnnp.56.6.684.
13. Joyce E, Blumenthal S, Wessely S. Memory,
attention, and executive function in chronic fatigue
syndrome. J Neurol Neurosurg Psychiatry, May,
1996; 60(5): 495-503. doi: 10.1136/jnnp.60.5.495.
14. Kane
RL,
Gantz
NM,
DiPinoRK.
Neuropsychological and psychological functioning
in chronic fatigue syndrome. Neuropsychiatry
Neuropsychol Behav Neurol, Jan, 1997; 10(1): 2531.
15. Krupp LB, Sliwinski M, Masur DM, Friedberg F,
Coyle PK. Cognitive functioning and depression inpatients with chronic fatigue syndrome and multiple
sclerosis. Arch Neurol, Jul, 1994; 51(7): 705-10.
doi: 10.1001/archneur.1994.00540190089021.
16. Lange G, Steffener J, Cook DB, Bly BM,
Christodoulou C, Liu WC, Deluca J, Natelson BH.
Objective evidence of cognitive complaints in
Chronic Fatigue Syndrome: a BOLD fMRI study ofverbal working memory. Neuroimage, Jun, 2005;
26(2):
513-24.
doi:
10.1016/j.neuroimage.2005.02.011.
17. Marcel B, Komaroff AL, Fagioli LR, Kornish RJ
2nd, Albert MS. Cognitive deficits in patients withchronic fatigue syndrome. Biol Psychiatry, Sep 15,
1996;40(6):
535-41. doi:
10.1016/00063223(95)00422-x.
18. Marshall PS, Forstot M, Callies A, Peterson PK,
Schenck CH. Cognitive slowing and working
memory difficulties in chronic fatigue syndrome.
Psychosom Med., Jan-Feb, 1997; 59(1): 58-66. doi:
10.1097/00006842-199701000-00008.
19. Michiels V, Cluydts R, Fischler B, Hoffmann G, Le
Bon O, De Meirleir K. Cognitive functioning inpatients with chronic fatigue syndrome. J Clin Exp
Neuropsychol, Oct, 1996; 18(5): 666-77. doi:
10.1080/01688639608408290.
20. Moss-Morris R, Petrie KJ, Large RG, Kydd RR.
Neuropsychological deficits in chronic fatigue
syndrome: artifact or reality? J Neurol Neurosurg
Psychiatry, May, 1996; 60(5): 474-7. doi:
10.1136/jnnp.60.5.474.
21. Ray C, Phillips L, Weir WR. Quality of attention inchronic fatigue syndrome: Subjective reports ofeveryday attention and cognitive difficulty, andperformance on tasks of focused attention. Br. J.
Clin. Psychol, 1993; 32 Pt 3: 357–364. doi:
10.1111/j.2044-8260.1993.tb01068.x.
22. Riccio M, Thompson C, Wilson B, Morgan DJ, Lant
AF.
Neuropsychologicalandpsychiatricabnormalities in myalgic encephalomyelitis: apreliminary report. Br J Clin Psychol, Feb, 1992;
31(1):
111-20.
doi:
10.1111/j.20448260.1992.tb00975.x.
23. Sandman CA, Barron JL, Nackoul K, Goldstein J,
Fidler F. Memory deficits associated with chronic
fatigue immune dysfunction syndrome. Biol

www.wjpmr.com│

Vol 8, Issue 7, 2022.

Psychiatry, Apr 15-May 1, 1993; 33(8-9): 618-23.
doi: 10.1016/0006-3223(93)90100-r.
24. Scheffers MK, Johnson R Jr, Grafman J, Dale JK,
Straus SE. Attention and short-term memory inchronic fatigue syndrome patients: an event-related
potential analysis. Neurology, Sep., 1992; 42(9):1667-75. doi: 10.1212/wnl.42.9.1667. PMID:
1513453.
25. Smith AP. Cognitive changes in Myalgic
Encepalomyelitis. In: A.Jenkins and J. Mowbray(eds), Postviral Fatigue Syndrome. Wiley: London,
1991; 179-1994.
26. Smith AP. Chronic fatigue syndrome andperformance. In: Handbook of Human Performance,
Vol.2: Health and performance. (eds) A.P. Smith &D.M. Jones. London: Academic Press, 1992; 261278.
27. Smith AP, Behan PO, Bell W, Millar K, Bakheit M.
Behavioural problems associated with the chronic
fatigue syndrome. British Journal of Psychology,
1993; 84: 411-423.
28. Thomas MA, Smith AP. An investigation into the
cognitive deficits associated with chronic fatigue
syndrome. The Open Neurology Journal, 2009; 3:
13-23. Doi: 10.2174/1874205X009030010013
29. Vercoulen JH, Bazelmans E, Swanink CM, Galama
JM, Fennis JF, van der Meer JW, Bleijenberg G.
Evaluating neuropsychological impairment inchronic fatigue syndrome. J Clin Exp Neuropsychol,
Apr,
1998;
20(2):
144-56.
doi:
10.1076/jcen.20.2.144.1160.
30. Vollmer-Conna U, Wakefield D, Lloyd A, Hickie I,
Lemon J, Bird KD, Westbrook RF. Cognitive
deficits in patients suffering from chronic fatigue
syndrome, acute infective illness or depression. Br J
Psychiatry, Oct, 1997; 171: 377-81. doi:
10.1192/bjp.171.4.377.
31. Smith AP. Memory impairments in chronic fatigue
syndrome patients. World Journal of Pharmaceuticaland Medical Research, 2022; 8(6): 50-54.
32. Smith AP. Cognitive impairments in Chronic
Fatigue Syndrome Patients: Choice reaction time,encoding of new information, response organisationand selective attention. World Journal of
Pharmaceutical and Medical Research, 2022; 8(4):27-36.
33. Smith AP, Pollock J, Thomas M, Llewelyn M,
Borysiewicz LK. 1996. The relationship between
subjective ratings of sleep and mental functioning in
healthy subjects and patients with Chronic Fatigue
Syndrome. Human Psychopharmacology, 1996; 11:
161-167.
34. Beck AT, Ward CH, Mendelson M, Mock J,
Erborough J. An inventory for measuring
depression. Archives of General Psychiatry, 1961; 4:
561-571.
35. Nelson HE. The National Adult Reading Test.
Windsor, Berks: NFER-Nelson, 1982.
36. Zevon MA, Tellegen A. The structure of moodchange: an idographic/nomothetic analysis. Journal│

ISO 9001:2015 Certified Journal│

58

Smith.

World Journal of Pharmaceutical and Medical Researchof Personality and Social Psychology, 1982; 43:
111-121.
37. Spielberger CD, Gorsuch RL, Lushene RE. STAI
Manual for the State-Trait Anxiety Inventory. Palo
Alto, CA: Consulting Psychologists Press, 1970.
38. Ray C, Weir WRC, Phillips S, Cullen S.
Development of a measure of symptoms in chronic
fatigue syndrome: The Profile of Fatigue RelatedStates (PFRS). Psychology and Health, 1992; 7: 2743.
39. Baddeley A. Working Memory. Oxford: Clarendon
Press, 1986.
40. Baddeley A, Emslie H, Nimmo-Smith I. Doors andPeople Test. Bury St Edmunds: Thames Valley Test
Company, 1994.

www.wjpmr.com│

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ISO 9001:2015 Certified Journal│

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