Chronic fatigue syndrome (CFS) is a debilitating disorder that has no agreed upon etiology or cure. Although sufferers report various physiological, psychological, and cognitive symptoms, debilitating fatigue represents the major characteristic of this disorder. In an attempt to investigate the basis of this fatigue, numerous studies have employed exercise tests in order to investigate physical function in CFS sufferers and typically report that these subjects have reduced exercise capabilities compared to matched, healthy control subjects (1,4,19,22,24). Proposals given to explain this reduced physical capacity include deconditioning (10,22), increased symptomatology (10), cardiac abnormalities (19), autonomic abnormality (4), and reduced oxidative delivery (17). Other researchers have suggested that the reduced physical capacity reported in CFS subjects was due to avoidance behaviors (6,23,24) based on a fear of exacerbating symptoms (23). However, we propose that physical function and its basis cannot be accurately determined in CFS unless subjects are appropriately matched with healthy controls. Of utmost importance is that subjects be matched according to their current activity levels; however, to date, most studies have ignored this aspect.
Having accounted for gender, age, height, and body mass, many studies that assessed physical function in CFS subjects enrolled control subjects who were classified as “sedentary.” However, the term “sedentary” is broad in definition and has been used by researchers to include control subjects who were involved in varying levels of exercise. For example, Sisto et al. (24) and LaManca et al. (16) enrolled control subjects who engaged in exercise no more than once a week, whereas McCully and Natelson (17) defined sedentary as pertaining to those who participated in regular exercise less than once a week for at least 6 months before testing. Alternatively, De Becker et al. (4) identified sedentary control subjects as those who performed sitting work and who participated in a maximum of 1 h of sports per week, whereas Gibson et al. (9) defined “sedentary” as pertaining to those individuals who did not participate in regular exercise. Studies by Montague et al. (19) and Fischer et al. (6) did not define the term sedentary, whereas Riley et al. (22) and Blackwood et al. (1) failed to use a “sedentary” criterion as a basis for matching subjects.
Criteria noted above to define “sedentary” control subjects ignores the possibility that although a subject may not participate in regular exercise, they might still be physically very active. For example, an individual who reads or watches television all day is classified under the same heading of “sedentary” as another individual who may care for active toddlers, shop, mow the lawns, and participate in gardening on a regular basis. This particular matching process promotes the possibility that the control subjects who participated in these studies, may on average, have been fitter than their CFS counterparts, consequently biasing results. Additionally, the inclusion of only “sedentary” control subjects ignores the possibility that some CFS subjects may still be involved in regular exercise, but at a lower level than their previous exercise regime, as is the case with some elite athletes who have CFS. Consequently, it is proposed that in order to accurately assess physiological function in CFS, control subjects should be matched to CFS subjects according to gender, age, height, body mass, as well as current activity levels.
Another area of concern with studies that assessed physical function in CFS sufferers is the common use of exercise tests that require subjects to provide a maximal effort (4,9,22,24). Although maximal oxygen consumption testing is recognized as the gold standard measurement of cardiorespiratory function, its use in a population that is characterized by severe fatigue and whose symptoms are typically reported to be exacerbated by exercise (29) may be detrimental, as well as deter potential subjects from participating in trials. This would suggest that submaximal exercise tests may be a more appropriate means to assess physical function in CFS subjects. Use of a submaximal exercise test may encourage more symptomatic CFS subjects to participate in research studies, which may result in the assessment of a greater range of physical capabilities and consequently provide results that are more representative of the CFS population. Additionally, in order to address the commonly reported cyclical nature of symptoms in CFS (11), all variables assessed were measured weekly over a 4-wk period and then averaged.
The aim of this study was to compare physical function in CFS sufferers to appropriately matched healthy control subjects, as assessed by a submaximal cycle exercise test that was performed on four separate occasions. As psychological factors have been proposed to play a role in physical capabilities, subjects were also required to answer questionnaires relating to anxiety, depression, and fatigue. We propose that CFS sufferers have a reduced exercise tolerance due to fear that excessive exercise will result in the exacerbation of symptoms. Consequently, we hypothesized that whereas physiological values at the end of each incremental level of the exercise test would be similar between CFS subjects and matched healthy control subjects that the CFS group would terminate their exercise test earlier than the healthy matched control group. It was also hypothesized that psychological scores would be significantly higher in the CFS group compared with the control group, indicating a greater prevalence of these symptoms.
Thirty-one CFS subjects (9 males, 22 females) aged between 22 and 64 yr were recruited from notices placed in local medical surgeries. Confirmation of CFS, as defined by the working case definition by Fukuda et al. (7) was supplied by each subject's medical doctor. The mean duration of symptoms was 2.9 (SD ± 1.55) yr (range 1–6 yr). Healthy control subjects were recruited from friends, associates, students, and staff on the university campus. Healthy control subjects were matched with CFS subjects according to age, gender, body mass, height, and current activity levels. All subjects gave written informed consent before entering the trials.
On arrival, all subjects were fitted with a HR monitor and had their height and body mass recorded. Weekly kilojoules for specific activities (that did not include any sitting or lying down activities) were determined using the Older Adult Exercise Status Inventory (OA-ESI; 21). Reliability and validity have been established for this questionnaire (21).
Before the exercise test, all subjects completed two psychological questionnaires. Mental and physical fatigue were assessed using a 11-item self-rating scale (3). This scale has acceptable internal consistency, face validity, and discriminant validity (3). Anxiety and depression were rated by the Hospital Anxiety and Depression Scale (HADS; 30). Reliability and validity have also been established for this scale (30).
The exercise protocol consisted of a submaximal cycle test known as the aerobic power index test (25), which has been shown to be reliable in a sedentary and a CFS population (intraclass correlation coefficient = 0.98 and 0.97, respectively) (27,28). The aerobic power index has a low power starting point that increases by 25 W every minute until an individual target heart rate (HR) based on 220 − age × 0.75 is reached (25). The primary outcome measure is the power output (W·kg−1) that coincides with a subject's individual target HR. This outcome is determined by interpolation techniques described in Telford et al. (25). If subjects were unable to reach their individual THR, then the watts per kilogram achieved during the last full minute of the exercise was recorded as the final power output. HR was recorded at the end of each minute of the exercise test, while ratings of perceived exertion (RPE), as measured by the Borg scale (2), were recorded 55 s into each minute of the exercise test. Oxygen consumption was analyzed continuously during the exercise test by a metabolic cart consisting of a computerized on-line system. Inspired air was measured by a Morgan Ventilometer Mark II 225A (P.K. Morgan, UK), while expired air was continuously sampled and recorded every 15 s by Applied Electrochemistry S-3A O2 and CD-3A CO2 analyzers (Pittsburgh, PA). The O2 and CO2 sensors were calibrated before and after each test using reference gases that had been gravimetrically determined on a previous occasion, while the Morgan ventilator was calibrated before and after each test according to the manufacturer's instructions. Analysis of oxygen consumption involved averaging each minute of data (collected every 15 s) and correcting for any analyzer or ventilatory drift. A similar interpolation procedure to that used to calculate Watts per kilogram at target HR was employed in order to determine oxygen uptake (mL·kg−1·min−1), RPE, and respiratory exchange ratio values that coincided with each individual's target HR. Reliability of these variables using this technique has previously been demonstrated in a sedentary and CFS population (27,28). Finally, blood lactate was measured before and three min after the completion of the exercise test.
All subjects were required to return for repeat testing at the same time of day, 1 wk apart for a further 3 wk. Subjects were required to follow the same daily routine 24 h before each test. On completion of the 4 wk of testing, all weekly results for physiological and psychological data were summed and then averaged. Two days after each testing session, subjects were contacted by phone in order to determine whether any relapse had occurred as a result of the exercise test. Ethics approval for this project was granted by the University of Western Australia Human Research Ethics Committee.
Demographic data relating to age, body mass, height, and activity levels were compared between the two groups during the first week of testing using a two-tailed paired samples t-test. Results recorded on the psychological questionnaires and averaged results recorded at the end of the exercise test were compared between the two groups using a one-tailed paired samples t-test. A one-tailed paired samples t-test was employed as the hypotheses proposed were of a directional nature. Averaged, absolute values for HR, respiratory exchange ratio, RPE and oxygen uptake (mL·kg−1·min−1) recorded at the end of each minute during the exercise test, were compared between participating CFS subjects and their matched controls using a two-tailed paired samples t-tests. Statistical significance was set at the 0.05 level. All statistical procedures employed the Statistical Package for the Social Sciences (SPSS), version 11.0.
Comparison of demographic data between groups showed that the two groups were similar (Table 1). Results showed no significant differences between the groups for age, body mass, height, or activity levels. Additionally, comparison of averaged resting physiological values also demonstrated similar results between the two groups, except for diastolic BP which was significantly higher but within normal range in the CFS group (15). These results would suggest that the two groups were well matched.
Averaged absolute values for HR, oxygen uptake (mL·kg−1·min−1), respiratory exchange ratio, and RPE data recorded at the end of each of the first seven work levels between CFS subjects and their matched control subjects are shown in Figures 1–4. Seven incremental workloads (175 W) represented the highest work level completed by 3 of the 31 subjects from the CFS group. In contrast, eight control subjects were able to complete seven work levels with the highest level achieved by one member of this group being level 10 (250 W). Results at the end of each work level were similar between CFS subjects and their matched control subjects for HR, respiratory exchange ratio, and oxygen uptake (mL·kg−1·min−1). Conversely, RPE scores were significantly higher in the CFS group for every level assessed.
Comparison of absolute averaged physiological results recorded at the end of each incremental stage of the exercise test between the two groups that included data for all subjects who completed each level (as opposed to only paired data), also resulted in no significant differences between the two groups.
Of the 124 exercise tests attempted by CFS subjects, only 16 subjects were able to reach their target HR for all four tests, whereas the remaining 15 CFS subjects reached their target HR on 23 of the 60 remaining tests. The number of tests that subjects failed to achieve THR were spread evenly over the four testing sessions. Of the 37 exercise tests in which target HR was not achieved by CFS subjects, fatigue was given as the reason for the premature termination on 35 occasions, whereas muscle pain in the legs and fear of relapse were cited on the other two occasions. Muscle pain and fear of relapse were given as reasons for early termination during the first week of testing. Control subjects were able to achieve their target HR on all 124 exercise tests.
Comparison of end-point results recorded at target HR, or at the end of the last completed work level if target HR was not achieved, showed that the control group was capable of a significantly higher power output (W·kg−1) than the CFS group (P < 0.0005; Table 2). This greater ability to produce a higher power output was further reflected by significantly higher end of test results for net lactate production (P = 0.003), oxygen uptake (mL·kg−1·min−1; P < 0.0005), respiratory exchange ratio (P = 0.021), and HR values as a percentage of age predicted HRmax (P = 0.001; Table 2) by the control group. Conversely, end-point RPE scores divided by the end-point power output (W) were significantly lower in the control group (P < 0.0005; Table 2), indicating that this group found the exercise easier than the CFS group.
An association between CFS and psychological symptoms was supported by significantly higher scores recorded by the CFS group compared with the matched healthy control group for anxiety (P < 0.0005) and depression (P < 0.0005). Scores for mental and physical fatigue were also significantly higher in the CFS group (P < 0.0005 and P < 0.0005, respectively; Table 3).
The results of this study showed that physiological variables consisting of HR, respiratory exchange ratio, and oxygen uptake (mL·kg−1·min−1) recorded at the end of each work level of an incremental exercise test, were similar between CFS subjects and their matched controls, except for RPE, which was significantly higher in the CFS group for all work levels assessed. These results are supported by other studies that reported similar values between CFS and healthy control subjects at the end of submaximal stages of an incremental exercise test for oxygen uptake (mL·kg−1·min−1) (24), respiratory exchange ratio (24), RPE (24), and HR (1,24). However, these earlier studies did not match their subjects according to activity levels, which consequently casts doubt on the validity of their reported outcomes. This same concern applies to studies by Montague et al. (19), who reported lower HR values at the end of each submaximal stage of exercise for CFS subjects compared with controls and for Riley et al. (22), who reported significantly higher incremental submaximal HR values in CFS subjects compared with controls.
Conversely, physiological results recorded on the completion of the exercise task revealed that the CFS group had a significantly reduced exercise capacity compared to controls. These results are similar to those reported in other studies that assessed peak values associated with work capacity (4,6,10,20), HR (4,10,20), oxygen uptake (4,6,10), postexercise blood lactate (16,22), and respiratory exchange ratio values (4,10,24). Additionally, significantly higher RPE scores recorded at the end of an exercise test by CFS subjects have also been reported by numerous investigators (1,9,22,24).
Various proposals have been made to explain the reduced exercise tolerance in CFS subjects that include physiological abnormalities and deconditioning (4,10,17,19,22); however, Sisto et al. (24) suggest that the low exercise tolerance demonstrated in CFS subjects is most likely due to reluctance by these subjects to exercise to full capacity, despite reporting significantly higher RPE scores. This conjecture is also supported by Fischler et al. (6), who suggest that CFS subjects avoided demanding tasks.
Results from this study suggest that the reduced exercise capacity demonstrated in some CFS subjects may be due to the existence of an abnormal sense of effort in these subjects and/or a reluctance to exercise to the target HR possibly due to an underlying, yet unexpressed, fear of relapse. Lack of support for deconditioning is provided by lower peak HR values (as a percentage of age-predicted HRmax), as well as a lack of evidence for premature or increased anaerobic metabolism in the CFS group compared with the control group at the end of the exercise task. Additionally, similar physiological values recorded at rest and at the end of each submaximal stage of the exercise test for HR, RER and oxygen uptake (mL·kg−1·min−1) between CFS subjects and their matched controls would further suggest that deconditioning, as well as cardiac abnormalities, autonomic impairment, and reduced oxidative delivery were not primarily responsible for group differences.
Fear that exercise would result in a relapse was demonstrated in CFS subjects by Vercoulen et al. (26), who reported that CFS subjects had strong expectations that activity would produce fatigue and that such expectations were related to low activity levels. Additionally, Mullis et al. (20) reported that many CFS subjects about to participate in an incremental exercise test to exhaustion expressed concern that the excessive activity would be detrimental to their health. Another study by Silver et al. (23) reported a positive correlation between high preexercise scores for anxiety in CFS subjects with reduced distance traveled on a cycle ergometer by these subjects. Anxiety in these subjects was reported by Silver et al. (23) to be related to fearful beliefs that the exercise would result in the exacerbation of symptoms. Reluctance by some CFS subjects to work to their full exercise capacity was demonstrated in our study by absolute peak RPE values reported by CFS subjects who ended their exercise test prematurely that ranged from 10 (just below “fairly light”) to 20 (“maximal” effort) and averaged 14.94 ± 1.86, (just below “hard”). These scores suggest that many of these subjects did not perceive their final work level as associated with a maximal effort. Additionally, although fear of relapse was only reported once as a reason for the early termination of the exercise test in our study, it is possible that this reason may have been an underlying but an unexpressed rationale behind the premature termination of the exercise test by some other subjects. Subjects may have felt that “fatigue” or “muscle pain” represented more “acceptable” reasons to justify the early cessation of their exercise test. Further evidence for “fear of relapse” being a reason for the premature termination of the exercise task by some CFS subjects is provided by the significantly higher anxiety scores recorded by CFS subjects compared to control subjects before the exercise test. Of importance is that numerous researches have suggested that fear of relapse, which typically results in avoidance behaviors, has a role in the maintenance and perpetuation of symptoms in CFS after the initial trigger has resolved (5,29).
A reduced exercise tolerance in the CFS group compared with the matched control group in our study is supported by significantly higher RPE scores reported by the CFS group at the end of every incremental level of the exercise test. These inflated values suggest an abnormality in the mechanisms that constitute effort sense in CFS sufferers.
Sense of effort has been proposed to result from a mismatch between the efferent copy of the motor command (corollary discharge) and sensory input (12). A disproportionate mismatch between neural signals, as a result of augmented or attenuated afferent or efferent signals, may occur for a number of reasons in CFS subjects. For example, effort sensation may be amplified by greater attention to physical and mental function paid to these mediators by CFS sufferers who vigilantly monitor symptoms (29). Additionally, loss of automatic functioning, as a result of inactivity, may result in CFS subjects devoting more attention to motor and somatosensory feedback during activity (1), consequently resulting in a gain in afferent inflow and a concomitant increase in effort sense.
A gain in effort sensation may also occur as a result of a reduced neural drive to the working muscles in CFS sufferers due to psychological factors such as fear of pain (10,14) and fear of relapse (23). This can result in a lack of motivation (10), which may consequently give rise to the habitual inhibition or reduced facilitation of motor unit recruitment (18). Reduced neural activation to the working muscles was demonstrated in CFS subjects by Kent-Braun et al. (14) using twitch interpolation methods during maximal voluntary contractions. The presence of significantly higher psychological symptoms in CFS subjects was demonstrated in our study and supports numerous other studies that assessed fatigue (1,8,13,16), depression (1,13), and anxiety (1,13,23) before either exercise or neuropsychological testing. Conversely, Fulcher and White (8) reported similar preexercise depression and anxiety scores between CFS and healthy control subjects; however, these results are most likely due to the exclusion of CFS subjects who had been diagnosed with a current psychiatric disorder.
Alternatively, an abnormal sense of effort may be due to a lower sensory threshold that occurs as a result of the severe restrictions placed on physical and mental activities by CFS sufferers when symptoms first appear (9). Gibson et al. (9) further suggest that a lower sensory threshold can result in CFS subjects “adding onto” the subjective feeling of fatigue and effort sensations felt at rest and during exercise.
Further studies that employ a graded exercise regime and/or cognitive behavioral therapy in an attempt to alleviate fear of exercise and consequent avoidance behaviors, as well as reduced sense of effort through improved automaticity and a possible increase in the sensory threshold are needed in order to determine whether this has an effect on exercise tolerance and function in CFS sufferers.
This study showed that physiological values recorded at the end of the first seven stages of an incremental exercise test were similar between CFS subjects and appropriately matched healthy control subjects. However, CFS subjects exhibited a reduced ability to reach a target HR based on 75% of age-predicted HRmax. It is proposed that this reduced exercise tolerance was attributed to avoidance behaviors associated with fear of relapse, as well as an abnormal sense of effort.
1.Blackwood, S., S. MacHale, M. Power, G. Goodwin, and S. Lawrie. Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. J. Neurol. Neurosurg. Psychiatr.
2.Borg, G. Psychophysical bases of perceived exertion. Med. Sci. Sports Exerc.
3.Chalder, T., G. Berelowitz, T. Pawlikowska, et al. Development of a fatigue scale. J. Psychol. Res.
4.De Becker, P., J. Roeykens, M. Reynders, N. McGregor, and D. De Meirleir. Exercise capacity in chronic fatigue syndrome. Arch. Int. Med.
5.Deale, A., and A. Davis. Chronic fatigue syndrome: evaluation and management. J. Neuropsychiatr.
6.Fischler, B., P. Dendale, V. Michiels, R. Cluydts, L. Kaufman, and K. De Meirleir. Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology. J. Psychol. Res.
7.Fukuda, K., S. Straus, I. Hickie, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann. Int. Med.
8.Fulcher, K. Y., and P. D. White. Strength and physiological response to exercise in patients with chronic fatigue syndrome. J. Neurol. Neurosurg. Psychiatr.
9.Gibson, H., N. Carroll, J. Clague, and R. Edwards. Exercise performance and fatiguability in patients with chronic fatigue syndrome. J. Neurol. Neurosurg. Psychiatr.
10.Inbar, O., R. Dlin, A. Rotstein, and B. J. Whipp. Physiological responses to incremental exercise in patients with chronic fatigue syndrome. Med. Sci. Sports Exerc.
11.Jason, L. A., C. P. King, E. L. Frankenberry, et al. Chronic fatigue syndrome: assessing symptoms and activity levels. J. Clin. Psychol
. 55:411–424, 1999.
12.Jones, L.A. The senses of effort and force during fatiguing contractions. Adv. Exp. Med. Biol.
13.Joyce, E., S. Blumenthal, and S. Wessely. Memory, attention, and executive function in chronic fatigue syndrome. J. Neurol. Neurosurg. Psychiatr.
14.Kent-Braun, J., K. Sharma, M. Weiner, B. Massie, and R. Miller. Central basis of muscle fatigue in chronic fatigue syndrome. Neurology
15.Kingwell, B. A., and G. L. Jennings. Effect of walking and other exercise programs upon blood pressure in normal subjects. Med. J. Aust.
16.LaManca, J., S. A. Sisto, X. Zhou, et al. Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion. J. Clin. Immunol.
17.McCully, K., and B. Natelson. Impaired oxygen delivery to muscle in chronic fatigue syndrome. Clin. Sci
. 97:603–608, 1999.
18.Miller, T. A., G. M. Allen, and S. C. Gandevia. Muscle force, perceived and voluntary activation of the elbow flexors assessed with sensitive twitch interpolation in fibromyalgia. J. Rheumatol.
19.Montague, T. J., T. J. Marrie, G. A. Klassen, D. J. Bewick, and B. M. Horacek. Cardiac function at rest and with exercise in the chronic fatigue syndrome. Chest
20.Mullis, R., I. T. Campbell, A. J. Weardon, R. K. Morriss, and D. J. Pearson. Prediction of peak oxygen uptake in chronic fatigue syndrome. Br. J. Sports Med.
21.O'Brien Cousins, S. An older adult exercise status inventory: reliability and validity. J. Sport Behav.
22.Riley, M., C. O'Brien, D. McCluskey, N. Bell, and D. Nicholls. Aerobic work capacity in patients with chronic fatigue syndrome. Br. Med. J.
23.Silver, A., M. Haeney, P. Vijayadurai, D. Wilks, M. Pattrick, and C. J. Main. The role of fear of physical movement and activity in chronic fatigue syndrome. J. Psychosom. Res.
24.Sisto, S. A., J. LaManca, D. L. Cordero, et al. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am. J. Med.
25.Telford, R. D., B. R. Minikin, A. G. Hahn, and L. A. Hooper. A simple method for the assessment of general fitness: the tri-level profile. Aust. J. Sci. Med. Sport
26.Vercoulen, J., E. Bazelmans, C. Swanink, et al. Physical activity in chronic fatigue syndrome: assessment and its role in fatigue. J. Psychol. Res.
27.Wallman, K., C. Goodman, A. Morton, et al. Test-retest reliability of the aerobic power index component of the tri-level fitness profile in a sedentary population. J. Sci. Med. Sport
28.Wallman, K., A. Morton, C. Goodman, et al. Reliability studies of the aerobic power index submaximal exercise test in a CFS population. J. Chronic Fatigue Syndr.
29.Wessely, S., M. Hotopf, and M. Sharpe. Chronic Fatigue and Its Syndromes.
London: Oxford University Press, 1999, p. 383.
30.Zigmond, A., and R. Snaith. The hospital anxiety and depression scale. Acta Physiol. Scand.
Keywords:©2004The American College of Sports Medicine
EXERCISE; PHYSICAL FUNCTION; ACTIVITY; AVOIDANCE BEHAVIORS