Fatigue is a common and disabling symptom in patients with multiple sclerosis (MS), but its pathogenesis is still poorly understood and consequently evidence-based treatment options are limited. Bol et al. (J Behav Med 33(5):355–363, 2010) suggested a new model, which explains fatigue in MS from a biopsychosocial perspective, including cognitive-behavioral factors. For purposes of generalization to clinical practice, cross-validation of this model in another sample of 218 patients with MS was performed using structural equation modeling. Path analysis indicated a close and adequate global fit (RMSEA = 0.053 and CFI = 0.992). The cross-validated model indicates a significant role for disease severity, depression and a fear-avoidance cycle in explaining MS-related fatigue. Modifiable factors, such as depression and catastrophizing thoughts, propose targets for treatment options. Our findings are in line with recent evidence for the effectiveness of a new generation of cognitive behavioral therapy, including acceptance and mindfulness-based interventions, and provide a theoretical framework for treating fatigue in MS.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Aaronson, N. K., Muller, M., Cohen, P. D., Essink-Bot, M.-L., Fekkes, M., Sanderman, R., et al. (1998). Translation, validation, and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations. Journal of Clinical Epidemiology, 51, 1055–1068.
Alberts, M., Smets, E., Vercoulen, J., Garssen, B., & Bleijenberg, G. (1997). ‘Verkorte vermoeidheidsvragenlijst’: een practisch hulpmiddel bij het scoren van vermoeidheid. Nederlands Tijdschrift voor Geneeskunde, 141, 1526–1530.
Asano, M., Berg, E., Johnson, K., Turpin, M., & Finlayson, M. L. (2014). A scoping review of rehabilitation interventions that reduce fatigue among adults with multiple sclerosis. Disability and Rehabilitation, 37(9), 729–738.
Bakshi, R., Shaikh, Z., Miletich, R., Czarnecki, D., Dmochowski, J., Henschel, K., et al. (2000). Fatigue in multiple sclerosis and its relationship to depression and neurologic disability. Multiple Sclerosis, 6, 181–185.
Bol, Y., Duits, A. A., Hupperts, R. M., Vlaeyen, J. W., & Verhey, F. R. (2009). The psychology of fatigue in patients with multiple sclerosis: A review. Journal of Psychosomatic Research, 66, 3–11.
Bol, Y., Duits, A. A., Lousberg, R., Hupperts, R. M., Lacroix, M. H., Verhey, F. R., et al. (2010). Fatigue and physical disability in patients with multiple sclerosis: A structural equation modeling approach. Journal of Behavioral Medicine, 33, 355–363.
Brañas, P., Jordan, R., Fry-Smith, A., Burls, A., & Hyde, C. (2000). Treatments for fatigue in multiple sclerosis: A rapid and systematic review. Health Technology Assessment (Winchester, England), 4, 1.
CBO. (2013). Richtlijn multipele sclerose 2012. Houten: Bohn Stafleu Van Loghum.
Compston, A., & Coles, A. (2008). Multiple sclerosis. The Lancet, 372, 1502–1517. doi:10.1016/S0140-6736(08)61620-7
Crombez, G., Eccleston, C., Van Damme, S., Vlaeyen, J. W., & Karoly, P. (2012). Fear-avoidance model of chronic pain: The next generation. The Clinical Journal of Pain, 28, 475–483.
Feinstein, A. (2011). Multiple sclerosis and depression. Multiple Sclerosis Journal, 17, 1276–1281.
Giovannoni, G. (2006). Multiple sclerosis related fatigue. Journal of Neurology, Neurosurgery and Psychiatry, 77, 2–3.
Hadjimichael, O., Vollmer, T., & Oleen-Burkey, M. (2008). Fatigue characteristics in multiple sclerosis: The North American Research Committee on Multiple Sclerosis (NARCOMS) survey. Health and Quality of Life Outcomes, 6, 100. doi:10.1186/1477-7525-6-100
Hind, D., Cotter, J., Thake, A., Bradburn, M., Cooper, C., Isaac, C., et al. (2014). Cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: A systematic review and meta-analysis. BMC Psychiatry, 14, 5.
Hirtz, D., Thurman, D., Gwinn-Hardy, K., Mohamed, M., Chaudhuri, A., & Zalutsky, R. (2007). How common are the “common” neurologic disorders? Neurology, 68, 326–337.
Honarmand, K., & Feinstein, A. (2009). Validation of the Hospital Anxiety and Depression Scale for use with multiple sclerosis patients. Multiple Sclerosis, 15(12), 1518–1524. doi:10.1177/1352458509347150.
Hoogerwerf, A. E., Bol, Y., Lobbestael, J., Hupperts, R. M., & van Heugten, C. M. Mindfulness based cognitive therapy is feasible and effective in severely fatigued patients with Multiple Sclerosis: A waiting list controlled study (submitted).
Horemans, H. L., Nollet, F., Beelen, A., & Lankhorst, G. J. (2004). A comparison of 4 questionnaires to measure fatigue in postpoliomyelitis syndrome. Archives of Physical Medicine and Rehabilitation, 85, 392–398.
Huber, P. J. (1967). The behavior of maximum likelihood estimates under nonstandard conditions. Paper presented at the proceedings of the fifth Berkeley symposium on mathematical statistics and probability.
Knoop, H., Van Kessel, K., & Moss-Morris, R. (2011). Which cognitions and behaviours mediate the positive effect of cognitive behavioural therapy on fatigue in patients with multiple sclerosis? Psychological Medicine, 42, 205–213.
Kos, D., Kerckhofs, E., Nagels, G., & D’Hooghe, M. (2008). Origin of fatigue in multiple sclerosis: Review of the literature. Neurorehabilitation and Neural Repair, 22, 91–100.
Kurtzke, J. F. (1983). Rating neurologic impairment in multiple sclerosis an expanded disability status scale (EDSS). Neurology, 33, 1444.
Lukkahatai, N., & Saligan, L. N. (2013). Association of catastrophizing and fatigue: A systematic review. Journal of Psychosomatic Research, 74, 100–109.
Maier, S., Balasa, R., Buruian, M., Maier, A., & Bajko, Z. (2015). Depression in multiple sclerosis—Review. Romanian Jounal of Neurology, 14, 22.
Miller, R. P., Kori, S. H., & Todd, D. D. (1991). The tampa scale. Unpublished report. Tampa, FL.
Minden, S. L., Frankel, D., Hadden, L., Perloff, J., Srinath, K. P., & Hoaglin, D. C. (2006). The Sonya Slifka longitudinal multiple sclerosis study: Methods and sample characteristics. Multiple Sclerosis, 12, 24–38. doi:10.1191/135248506ms1262oa
Moss-Morris, R., Dennison, L., Landau, S., Yardley, L., Silber, E., & Chalder, T. (2012). A randomized controlled trial of cognitive behavioral therapy (CBT) for adjusting to multiple sclerosis (the saMS trial): Does CBT work and for whom does it work? Journal of Consulting and Clinical Psychology, 81, 251–262. doi:10.1037/a0029132
Muthén, L. K., & Muthén, B. O. (1998–2012). Mplus user’s guide (7th ed.). Los Angeles, CA: Muthén & Muthén.
Osman, A., Barrios, F. X., Gutierrez, P. M., Kopper, B. A., Merrifield, T., & Grittmann, L. (2000). The Pain Catastrophizing Scale: Further psychometric evaluation with adult samples. Journal of Behavioral Medicine, 23, 351–365.
Patrick, E., Christodoulou, C., & Krupp, L. (2009). Longitudinal correlates of fatigue in multiple sclerosis. Multiple Sclerosis, 15, 258–261.
Polman, C. H., Reingold, S. C., Edan, G., Filippi, M., Hartung, H. P., Kappos, L., et al. (2005). Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Annals of Neurology, 58, 840–846.
Pucci, E., Branas, P., D’Amico, R., Giuliani, G., Solari, A., & Taus, C. (2007). Amantadine for fatigue in multiple sclerosis. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD002818.pub2.
Rabinowitz, A. R., & Arnett, P. A. (2009). A longitudinal analysis of cognitive dysfunction, coping, and depression in multiple sclerosis. Neuropsychology, 23, 581.
Rietberg, M., Van Wegen, E., & Kwakkel, G. (2010). Measuring fatigue in patients with multiple sclerosis: Reproducibility, responsiveness and concurrent validity of three Dutch self-report questionnaires. Disability and Rehabilitation, 32, 1870–1876.
Silver, A., Haeney, M., Vijayadurai, P., Wilks, D., Pattrick, M., & Main, C. (2002). The role of fear of physical movement and activity in chronic fatigue syndrome. Journal of Psychosomatic Research, 52, 485–493.
Strober, L. B., & Arnett, P. A. (2005). An examination of four models predicting fatigue in multiple sclerosis. Archives of Clinical Neuropsychology, 20, 631–646.
Sullivan, M. J., Bishop, S. R., & Pivik, J. (1995). The pain catastrophizing scale: Development and validation. Psychological Assessment, 7, 524.
Ukueberuwa, D. M., & Arnett, P. A. (2014). Evaluating the role of coping style as a moderator of fatigue and risk for future cognitive impairment in multiple sclerosis. Journal of the International Neuropsychological Society, 20, 751–755.
Van Kessel, K., & Moss-Morris, R. (2006). Understanding multiple sclerosis fatigue: A synthesis of biological and psychological factors. Journal of Psychosomatic Research, 61, 583–585.
van Kessel, K., Moss-Morris, R., Willoughby, E., Chalder, T., Johnson, M. H., & Robinson, E. (2008). A randomized controlled trial of cognitive behavior therapy for multiple sclerosis fatigue. Psychosomatic Medicine, 70, 205–213.
Vercoulen, J., Alberts, M., & Bleijenberg, G. (1999). De checklist individuele spankracht (CIS). Gedragstherapie, 32, 131–136.
Vlaeyen, J. W., Kole-Snijders, A. M., Rotteveel, A. M., Ruesink, R., & Heuts, P. H. (1995). The role of fear of movement/(re) injury in pain disability. Journal of Occupational Rehabilitation, 5, 235–252.
Wu, S., Mead, G., Macleod, M., & Chalder, T. (2015). Model of understanding fatigue after stroke. Stroke, 46, 893–898.
Zedlitz, A. M., Rietveld, T. C., Geurts, A. C., & Fasotti, L. (2012). Cognitive and graded activity training can alleviate persistent fatigue after stroke a randomized, controlled trial. Stroke, 43, 1046–1051.
Zigmond, A. S., & Snaith, R. P. (1983). The hospital anxiety and depression scale. Acta Psychiatrica Scandinavica, 67, 361–370.
We would like to thank all the patients who took part in this study; the therapists, psychological assistants and MS nurses of Zuyderland Medical Center; Dr. Myreen Moors for her effort in gathering and monitoring the data acquisition; Prof. Dr. Raymond Hupperts for his kind cooperation and time investment.
Conflict of interest
Melloney L. M. Wijenberg, Sven Z. Stapert, Sebastian Köhler and Yvonne Bol declare that they do not have any conflict of interest.
Human and animal rights and Informed consent
All procedures were approved by and in accordance with the ethical standard of the medical ethics committee of Zuyderland Medical Center and with the 1964 Helsinki declaration and its later amendments. Informed consent was obtained from all patients for being included in the study.
About this article
Cite this article
Wijenberg, M.L.M., Stapert, S.Z., Köhler, S. et al. Explaining fatigue in multiple sclerosis: cross-validation of a biopsychosocial model. J Behav Med 39, 815–822 (2016). https://doi.org/10.1007/s10865-016-9749-3
- Multiple sclerosis
- Physical disability
- Structural equation modelling
- Biopsychosocial model