Introduction
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with an unknown pathogenesis and an unpredictable course. MS is considered to be one of the most common neurological disorders affecting young adults (Compston and Coles
2008) The clinical picture of MS is diverse and includes physical and neuropsychiatric symptoms (Feinstein
1999). Up to 90% of patients with MS complain of fatigue (Branas et al.
2000). Fatigue in MS patients is more severe and disabling compared to fatigue in healthy controls and several other somatic populations (De Ridder et al.
2004; Krupp
2006; Krupp et al.
1988,
1989; Penner et al.
2007; Trojan et al.
2007), and over two-thirds of MS patients characterize it as their most troubling symptom (Branas et al.
2000). The pathogenesis of MS-related fatigue is still poorly understood and treatment options are limited (Bol et al.
2009; Kos et al.
2008). In clinical practice, fatigue is often treated by both pharmacological and non-pharmacological interventions, such as exercise therapy and energy conservation strategies (Kos et al.
2008). However, the empirical evidence for effectiveness of these interventions is limited (Pucci et al.
2007; Rietberg et al.
2005; Solari et al.
2003; Steultjens et al.
2003).
From a traditional biomedical perspective, MS-related fatigue is considered to be a primary symptom of MS that is directly related to the severity of the disease. Although there is some evidence for underlying pathophysiological mechanisms, including inflammation, demyelinisation, axonal loss, and neuroendocrine dysregulation, these variables appear to explain only a small part of the variance of both MS-related fatigue and MS-related disability (Bol et al.
2009; Kos et al.
2008). More recently, a cognitive-behavioral approach has been proposed which suggests that fatigue is not perpetuated or worsened by the severity of the disease or associated symptoms, but by the individual’s interpretation of these symptoms (Skerrett and Moss-Morris
2006; Van Kessel and Moss-Morris
2006). Empirical evidence for such an approach has been found in cases of chronic fatigue syndrome (Deary et al.
2007; Nijs et al.
2004; Silver et al.
2002), cancer survivors (Donovan et al.
2007), and chronic pain (Arntz and Claassens
2004; Leeuw et al.
2007).
One of the key variables in recent cognitive-behavioral approaches of symptom reporting is the way information is interpreted. For example, catastrophic interpretations are characterized by exaggerated negative rumination, amplification of the symptoms, and helplessness (Leeuw et al.
2007; Sullivan et al.
1995), which are all associated with negative emotions. In particular, catastrophizing is associated with specific, symptom-related, fear which in turn incites avoidance behavior and in the long term contributes to disability (Andrea et al.
2004; Jacobsen et al.
2004; Nijs et al.
2004; Silver et al.
2002). There is also evidence that MS patients who catastrophize about their fatigue and who attribute their fatigue to their illness are more likely to focus their attention on signs of fatigue and to interpret the consequences of fatigue in terms of physical damage (Skerrett and Moss-Morris
2006). A second feature of a cognitive-behavioral approach is its focus on functioning in the presence of persistent symptoms such as pain and fatigue. There is evidence that the functional disability levels are more strongly influenced by the emotional responses to the symptoms than the symptoms themselves (e.g. Crombez et al.
1999).
The hypothesis of the cognitive-behavioral model was that patients who interpret their fatigue catastrophically, report more fatigue-related fear and avoidance, and hence are more physically disabled, depressed and fatigued (Skerrett and Moss-Morris
2006; Van Kessel and Moss-Morris
2006). In contrast, the biomedical model assigns a more prominent role to disease severity and depression in predicting the level of fatigue (Amato et al.
2001; Janardhan and Bakshi
2002; Merkelbach et al.
2002) and considers catastrophizing about fatigue, and fatigue-related fear and avoidance, to be consequences rather than precursors of physical disability.
In present study we compared a model based on a cognitive-behavioral approach with that based on a more traditional, biomedical approach. Given the merits of both approaches, a comparison of both approaches is not only interesting theoretically, but may also provide elements for a better care of patients with MS-related fatigue and disability. Using structural equation modeling (SEM), we compared the fit indices of our data according to both theoretical models. In line with evidence in other populations (Deary et al.
2007; Donovan et al.
2007; Leeuw et al.
2007; Nijs et al.
2004; Silver et al.
2002), we expected to find that the cognitive-behavioral model would show a better fit than the traditional biomedical model.
The results of this study may have clinical implications. The first, and so far only, randomized clinical trial of cognitive-behavioral therapy (CBT) in MS patients appeared to be more effective in reducing self-reported fatigue than relaxation therapy (Van Kessel et al.
2008). Not only fatigue, but also fatigue-related disability and depression showed a significant decrease. These results are in favor of a cognitive-behavioral approach to treat fatigue, but the theoretical assumptions of CBT were not formally tested yet. The focus of the present study is to test the underlying mechanisms of CBT. Insight into how the various relevant factors may affect one another, can help us to develop more responsive interventions to treat MS-related fatigue and disability.
Discussion
The aim of the current study was to test the assumptions of a cognitive-behavioral model by comparing these with those of a traditional biomedical model. In particular, we tested and explored the role of catastrophic (mis)interpretations on MS-related fatigue and physical disability. In contrast to the biomedical model, the cognitive-behavioral model’s main assumption is that fatigue is not perpetuated or worsened by disease severity or associated symptoms, but by the patient’s interpretation of these symptoms.
SEM revealed that neither of these models showed adequate fit of our data and the modification indices suggested an integrative approach. As such, the cognitive-behavioral model was subsequently modified by adding several theoretically meaningful relationships derived from the biomedical approach and deleting non-significant relationships. Although, the final model did not meet all preset fit criteria, it showed the best fit indices. The suboptimal fit of the final model could be due to the omitted-variable problem, which means that we failed to have included other relevant variables such as sleep problems, disease course, and medication use. Inclusion of such variables in future work may improve the fit indices. Even though some relevant variables may be lacking in the final model, its present structure is generally in line with that of the fear-avoidance model of chronic pain (Vlaeyen and Linton
2000; Leeuw et al.
2007) and with evidence for the joint contribution of biomedical and psychological factors in the prediction of pain and disability (Peters et al.
2005). The integrated model is notable for at least three main features: first, fatigue is associated with depression and physical disability. Second, physical disability is associated with disease severity and fatigue-related fear and avoidance behavior, and third, catastrophic interpretations about fatigue, -fueled by depression-, mediate the relationship between fatigue and fatigue-related fear and avoidance behavior.
Catastrophic interpretations of fatigue such as “When I am tired, this is a signal there is something wrong in my brain” and “When I am tired, this is a sign that my MS is getting worse” seemed to be a key factor and mediated the relationship between fatigue and fatigue-related fear and avoidance behavior. Hence, catastrophizing about fatigue may be an important target for cognitive-behavioral interventions during which dysfunctional fatigue-related thoughts can be challenged (e.g. Swain
2000). In this kind of cognitive treatment, patients are given the opportunity to test the credibility of their beliefs in catastrophic outcomes, and to correct these accordingly.
Furthermore, depression appeared to play an important role in our final model. Depression was a negative consequence of increased disability, and it directly contributed to fatigue and catastrophizing about fatigue. Depression is known to be the most common psychiatric disorder in MS, with an estimated prevalence ranging between 27 and 54% (Minden et al.
1987; Minden and Schiffer
1990; Sadovnick et al.
1996; Schiffer et al.
1983). Therefore, we recommend the inclusion of depression in screening procedures and treatment for fatigued MS patients.
In contrast to the fear-avoidance model in chronic pain, disease severity played a prominent role in our final model. Disease severity indirectly contributed to fatigue, through fatigue-related fear and avoidance behavior, and physical disability. MS patients with higher levels of disease severity seem to experience more fear-related cognitions, and hence more physical disability. One of the reasons why disease severity in MS has a prominent role in prediction of fatigue and disability may be that the disease and the disease-related symptoms of MS are much less ambiguous as compared other chronic illness conditions such as in patients with chronic pain and chronic fatigue syndrome.
While our results are in line with those of the first randomized clinical trial of cognitive-behavioral therapy (CBT) for fatigue in MS patients (Van Kessel et al.
2008), they also suggest that optimal treatment could be a combination of CBT and medical therapy. Given that most MS patients already receive medical treatment, more efforts should be directed towards the cognitive and behavioral aspects of fatigue. Since the CBT trial from Van Kessel e.a (2008), was rather non-specific and focusing—in only one session—on changing negative thoughts, our findings suggests that its effectiveness might be increased by better tailored CBT. Fatigued MS patients could benefit more if the target of CBT is on challenging idiosyncratic catastrophizing thoughts about fatigue and not negative thoughts in general. Such a treatment would be similar to exposure-based interventions for patients who report increasing pain-related fear (e.g. De Jong et al.
2005; Bailey et al.
2010).
There are several limitations to this study, which should be taken into account when interpreting the results and which may be addressed in future studies. First of all, the design is cross-sectional, making it impossible to draw firm conclusions about causal relationships between variables. Prospective and longitudinal studies are warranted to confirm causality. Secondly, because of our relatively small sample size, we were not able to split our sample in order to cross-validate our final model. Thirdly, we used postal questionnaires to collect our data. Although we had a favorable response rate for a postal questionnaire, we were not able to examine the differences between responders and non-responders. As a result, we cannot exclude the fact that a potential selection bias might have interfered with the present results. Fourthly, our measures for catastrophizing about fatigue (FCS), and fatigue-related fear and avoidance behavior (TSK-F), are adaptations of valid instruments. Although both measures show excellent internal consistency, their reliability and validity need to be established further. Finally, all data, including those on physical disability, were self-reported and therefore amenable to retrospective bias and social desirability effects. Furthermore, it is possible that strong associations between self-reported variables are the result of shared-method variance (Podsakoff et al.
2003). Future studies should also include more objective measures such as an accelerometer, which is a reliable and valid measure of daily activity levels (Bassett
2000; Ng and Kent-Braun
1997).
Despite the limitations described above, this study shows that not only severity of disease, but also cognitive-behavioral factors, such as catastrophizing about fatigue and fatigue-related fear and avoidance behavior, have to be considered when trying to explain fatigue and physical disability in MS patients. As such our results suggest that an integrated approach, would be beneficial in the treatment of fatigue in MS patients.