Introduction

Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling condition characterized by severe unexplained fatigue and a mixed profile of symptoms such as sore throat, painful/swollen lymph nodes, muscle pain, joint pain, headaches, unrefreshing sleep, post-exertional malaise and cognitive difficulties (K. Fukuda et al., 1994). Understanding this condition continues to be problematic as a result of its heterogeneity (Jason, Corradi, Torres-Harding, Taylor, & King, 2005). One fundamental impediment to diagnostic, assessment, and treatment efficacy research is the definition of fatigue itself. Researchers have noted that the subjective experience of fatigue may differ between individuals as well as within individuals themselves (Gielissen et al., 2007; Smets, Garssen, Bonke, & De Haes, 1995). Individuals with ME/CFS frequently report the occurrence of several distinct fatigue states that might diverge from commonplace perceptions of the fatigue among the general population.

Fatigue has been measured using a single, finite symptom as well as in more multi dimensional approaches (Chalder et al., 1993). Early studies on fatigue measurement adhered to the former model (Brook et al., 1979; Krupp, LaRocca, Muir-Nash, & Steinberg, 1989; Montgomery, 1983; Pearson & Byars, 1956) whereas more recent studies have utilized the latter model (Gielissen et al., 2007; Ray, Weir, Phillips, & Cullen, 1992; Smets et al., 1995). Although for clinical and research purposes, a single measure of fatigue may be expedient, empirical evidence supports the measurement of fatigue in multi-dimensional ways (Dechene, Friedberg, McKenzie, & Fontanetta, 1994; Gielissen et al., 2007; Jason et al., 2002; Libman et al., 2008; Nisenbaum, Reyes, Mawle, & Reeves, 1998; Smets et al., 1995). A consensus model has yet to emerge, but there are some consistencies between existing typologies. For example, the distinction between "physical" fatigue and "mental" fatigue is one with general acceptance among researchers as reflected in existing fatigue instruments (Chalder et al., 1993; Ray et al., 1992; Smets et al., 1995) and ME/CFS typologies (Jason et al., 2002).

These typologies of fatigue in ME/CFS have not always been able to discriminate the variety of types of fatigue experienced. The distinction between the experience of fatigue for persons with and without this condition is important for several reasons. First, understanding fatigue states unique to ME/CFS would be helpful for diagnosticians that lack biological testing and must rely on patient self-report. Second, incorporating measures of fatigue types could clarify patient profiles, and researchers have already begun working towards empirical methods of diagnosis (Jason, Corradi, & Torres-Harding, 2007). Third, examining the properties of each fatigue aspect may aid clinicians in creating individualized treatment options. Finally, types of fatigue unique to persons with ME/CFS could provide a language that patients could use to communicate with family, friends, and health-care providers about their condition; a language that the patient community feels is lacking (Wall, 2000).

The Fatigue Scale (Chalder et al., 1993) is one of the most widely used measures assessing fatigue in research with ME/CFS. Recently, Goudsmit, Stouten, and Howes (in press) found patients with ME/CFS recorded comparatively high scores on the Fatigue Scale. In addition, they found that there was a marked overlap in fatigue scores between those patients who rated themselves as moderately or severely ill. The authors concluded that the Fatigue Scale is not sensitive enough to reflect changes in functioning, as those with a maximum score at baseline will not be able to record an increase in fatigue following an intervention. In addition, the Fatigue Scale has not demonstrated efficacy in discriminating between different individuals with ME/CFS and those with primary depression (Friedberg & Jason, 1998). Stouten (2005) has also indicated that many frequently used fatigue scales do not accurately measure the severe fatigue that is characteristic of ME/CFS. Several recent investigations have compiled data that suggests a different fatigue structure for individuals with ME/CFS as compared to normal populations. Gielissen and colleagues (2007) developed the Fatigue Quality List (FQL), which is an 18-item adjective checklist that measures the affective experience of fatigue. Using factor analysis, these 18 adjectives resulted in four factors. Interestingly, one of the factors identified was 'pleasant', which was found to have higher scores for healthy populations as opposed to clinical populations. Additionally, higher scores were found in the ME/CFS group on the other three factors (i.e., Exhausting, Frustrating, and Frightening). This study did not assess the actual experience or symptoms of fatigue, but rather the affective responses associated with fatigue.

In another study, Libman et al. (2008) asked a group of healthy participants and a group of participants diagnosed with ME/CFS to make a list of adjectives to describe their fatigue. The resulting lists were separated into 18 different categories, and it was found that the participants with ME/CFS were present in more categories and used more descriptors for each category. Also, the healthy group used more positive adjectives describing their fatigue, such as "temporary," "comfortable," and "sleepy." This study employed non-parametric methods, so they were not able to provide a factor analysis to uncover the underlying dimensions within these constructs. Finally, Fukuda et al. (2008) developed a new fatigue scale that assessed the factors of Fatigue, Anxiety/Depression, Cognitive, Pain, Overwork, Autonomic, Sleep, and Infection. However, only Anxiety/Depression, Pain, and Infection were able to discriminate CFS-fatigue patients from non-CFS-fatigue patients. This questionnaire, however, is somewhat long at 64 items, and 11 items involve anxiety or depression constructs which are not physical items and might represent different dimensions than fatigue.

The present study assessed the symptoms of fatigue using factor analysis among patients with ME/CFS versus control individuals. We developed the ME/CFS Fatigue Types Questionnaire (MFTQ), a 22-item scale designed to measure the duration, severity and frequency of different fatigue-related sensations and symptoms. Item generation was guided by existing typologies Specifically, we generated fatigue items that encompassed the following dimensions: lack of energy resources needed for daily functioning; over stimulation of the mind or body without the available energy to act out the mental or physiological excited state; exhaustion or interruption related to everyday cognitive processes; tiredness that is associated with physical symptoms commonly seen in cases of influenza; and abnormal exhaustion following physical activity. We hypothesized there would be several fatigue factors in the individuals with ME/CFS but that this differentiation would not occur with our control group. Validity analyses were also conducted by comparing the factor scores of the new instrument with more traditional measures of fatigue.

Method

Results

Discussion

Overall, the MFTQ appears to be a reliable and valid measure of fatigue types in individuals with ME/CFS. The five-factor structure confirmed in the ME/CFS sample suggests that the symptom of fatigue in this illness is a multi-dimensional entity that is distinct from the generalized form of fatigue experienced by general population. These factors explained an adequate amount of the variance. In contrast, among the control group, only one factor emerged, and it explained considerably less variance. It appears that the items, designed for individuals with ME/CFS, did not account for a large percent of the variance among the controls. Therefore, among members of the general population, this new fatigue scale does not measure what most individuals perceive as fatigue. However, the findings suggest that the MFTQ does differentiate fatigue symptoms for those who have ME/CFS.

Because of the subjectivity of fatigue, there has been inconsistency in the language used to describe this construct. Several researchers and professionals agree that the lack of a common vocabulary may result in clinicians' doubts concerning their prescribed treatment and unsatisfactory care for the patient (Gielissen et al., 2007; Shapiro, 1998). The problem does not appear to be a lack of fatigue descriptors (Libman et al., 2008), but rather a considerable amount of definitional overlap for different fatigue terms (Shapiro et al., 2002).

This study therefore attempted to draw conceptual distinctions between fatigue synonyms and make this information accessible for clinicians to use in practice. It is equally important that the language used is also disease-specific for conditions in which fatigue is a primary symptom. In the present study, we attempted to use terms already employed by individuals with ME/CFS to label the hypothesized fatigue types (e.g. "brain fog"). Comments among members of ME/CFS group indicated the terms were generally favorable. Controlling for the socio-demographic variables, the ME/CFS group had significantly worse factor scores than the control group. These findings suggest that the MFTQ differentiates between individuals with ME/CFS versus those from the general population. It should be noted that the two samples differed on several demographic variables that were controlled for in the analyses. Still, it could be argued that some of the differences between the two groups were due to socio-demographic differences. While it is true that we might have been able to recruit a comparison group of similar age, gender and ethnicity, there still would have been significant employment differences, given the health status of the ME/CFS group. In a sense, whenever a comparison is made between ME/CFS participants and a control group, there will be important differences between these groups that will be difficult to control.

As illustrated within Table 5, several of the more interesting significant differences between the ME/CFS versus control groups involved when one correlation was significant and the other was not significant. For example, there was a significantly higher correlation between the MFTQ Post-Exertional and PFRS Emotional Distress factors (r = .36) for the control group when compared to the ME/CFS group (r = .09), with the former correlation being significant and the latter not being significant. The MFTQ Post-Exertional factor, which measures unusual, persisting fatigue or malaise resulting from some type of effort, is distinct for ME/CFS patients from the Emotional Distress factor of the PFRS, which measures mood states such as depression, anxiety, and anger (Ray et al., 1992).

When people with ME/CFS report symptoms of post-exertional malaise, those symptoms are independent of emotional distress, but when the general population report what they think are post-exertional malaise symptoms, their symptoms of post-exertional malaise are significantly related to emotional distress. It is possible that because healthy individuals experience a relationship between emotional distress and post-exertional malaise, they might believe that these two domains are connected for themselves and by inference with patients with ME/CFS, when in fact it is not the case. This ultimately might blur the ability of healthy controls to understand the experience of post-extertional malaise for people with ME/CFS. Of interest, a similar pattern occurred with the MFTQ factor Energy and PFRS Emotional distress, with a significant difference in the correlations between the ME/CFS group and the controls. Again, it is possible that the general population experiences a relationship between emotional distress and energy problems, they might believe that patients with ME/CFS not only have this same connection, but it might also be perceived by some as causal. In fact, the lack of a relationship between energy problems and emotional distress suggests that these two domains are not related among patients with ME/CFS. This observation is further supported by the finding that the Total MFTQ score among the control group is more highly related to emotional distress than among patients with ME/CFS.

Surprisingly, the Energy factor of the MFTQ, which logically should be related to the PFRS Fatigue factor (physical fatigue can also be thought of as having depleted energy reserves), did not show a significant correlation for the ME/CFS group (r = .05), yet a significantly stronger relationship was found for the control group (r = .35). This might seem like a contradiction to our main hypothesis that persons with ME/CFS are able to distinguish types of fatigue while control individuals cannot. However, a closer examination of the PFRS Fatigue factor items suggests that many different fatigue states are subsumed in this subscale and may have skewed the coefficients. For example, items such as "The slightest exercise making you physically tired" and "muscles feeling weak after slight exercise" denotes post-exertional fatigue that relates to the unusual fatigue or malaise resulting from exertion. Yet other items within the subscale are more closely related to the Energy factor of the MFTQ, such as "Feeling physically drained" and "Not having the physical energy to do anything", indicating a clear depletion of energy reserves that is unrelated to exercise or effort. Consequently, this suggests that the MFTQ may delineate finer shades of meaning when the word fatigue is used in the context of physical fatigue; shades of meaning that are more accessible to those who have ME/CFS. A similar inconsistent pattern emerged when correlating the MFTQ Brain Fog factor and the PFRS Fatigue factor. The correlation for the ME/CFS group (r = .15) was significantly lower than the control (r = .41). Similar reasons might have occurred for both the constructs of Energy and Brain Fog, as measured by the MFTQ, and the PFRS Fatigue factor.

The FSS, a measure of the impact fatigue has on one's functional ability, demonstrated stronger relationships for the MFTQ Post-Exertional factor for the ME/CFS group (r = .46) than the control group (r = .25). The FSS also had a stronger relationship with the MFTQ Energy for the ME/CFS group (r = .40) as opposed to the control group (r = .22). Logically, lower energy levels and more impairment following exertion should exhibit a strong relationship with a measure of functionality. Once again, when compared to controls, the ME/CFS group demonstrated relationships more consistent with the theoretical underpinnings of each scale subfactor. There were several limitations in the present study. Differences in socio-demographic variables among the samples, and low variance explained by the items for the control group have already been mentioned. In addition, the sample sizes for the two groups were unequal, and somewhat small for the ME/CFS group. However, some researchers posit that a minimum of 100 participants (Guadagnoli & Velicer, 1988) or a subject to variable (i.e. item) ratio of 5 or greater is sufficient for factor analysis, and both of these criteria were satisfied in the present study (Bryant & Yarnold, 1995). It could also be argued that because the university sample yielded only 1 factor, the responses in that sample might not support calculating 5 separate factor scores. However, we thought it useful to compare the ME/CFS group with the control group on these factor scores, as they help differentiate important domains of the fatigue experience for people with ME/CFS versus those who are among the general population, and provide estimates of construct validity. Finally, most of the correlations in Table 5 were quite modest suggesting that there is considerable measurement error in all of the scales used.

We chose an exploratory factor analysis rather than a confirmatory factor analysis as we did not feel that there were enough prior studies or theory development to be confident in our predicted factor structure. We were pleased to find out that many of our items loaded on our predicted factors, and subsequently recognized that readers might wonder why we had not used a confirmatory factor analysis from the start. However, a decision on what statistic was to be employed was made prior to data analysis, and we felt it inappropriate to use a confirmatory factor analysis following our use of the exploratory factor analysis.

The symptom of fatigue continues to be problematic for researchers and clinicians and remains a fruitful area for further investigation. The push for an empirical case definition of ME/CFS (Jason et al., 2007) underscores the need for the measurement of fatigue in clinical settings as well as research laboratories. Many fatigue instruments now exist that could serve this purpose though the refinement of these measures and development of new diagnostic materials is needed. As suggested by this study, the disabling fatigue experienced by individuals with ME/CFS differs from that associated with other illnesses or everyday activity, and thus steps must be taken to clarify the diverse nature of fatigue among patients with ME/CFS. Such clarification would not only provide improvement in diagnosis and illness management, but also serve to mitigate the stigma associated with ME/CFS as evidence would exist of a fatigue experience different from those related to over-exertion or depression. Although our study focused on practical diagnostic and descriptive issues related to this illness, it is important for scientists to accurately and unequivocally communicate the experience of this illness in order to fully inform the perceptions of doctors, patients, and outside observers.