The effect of depression on health-related quality of life is mediated by fatigue in persons with multiple sclerosis

Stephanie Rodgers, Zina Mary Manjaly, Pasquale Calabrese, Nina Steinemann, Marco Kaufmann, Anke Salmen, Andrew Chan, Jürg Kesselring, Christian P. Kamm, Jens Kuhle, Chiara Zecca, Claudio Gobbi, Viktor von Wyl, Vladeta Ajdacic-Gross

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9 Scopus citations


The interrelations between fatigue, depression and health-related quality of life (HRQoL) in persons with multiple sclerosis (PwMS) are complex, and the directionality of the effects is unclear. To address this gap, the current study used a longitudinal design to assess direct and indirect effects of fatigue and depression on HRQoL in a one-year follow-up survey. A sample of 210 PwMS from the nationwide Swiss MS Registry was used. HRQoL was assessed using the European Quality of Life 5-Dimension 5-Level questionnaire. Path analysis on HRQoL, with fatigue and depression as predictors, was applied. Fatigue was measured by the Modified Fatigue Impact Scale (MFIS), including physical, cognitive and psychosocial subscales, and non-somatic depressive symptomatology was examined with the Beck Depression Inventory-Fast Screen (BDI-FS). Fatigue acted as a fully mediating variable (B = −0.718, SE = 0.253) between non-somatic depressive symptomatology and HRQoL. This indirect effect became apparent in the physical (B = −0.624, SE = 0.250), psychosocial (B = −0.538, SE = 0.256) and cognitive subscales (B = −0.485, SE = 0.192) of fatigue. In contrast, nonsomatic depressive symptomatology did not act as a mediator. Our findings provide novel and clinically relevant longitudinal evidence showing that the debilitating effect of non-somatic aspects of depression on HRQoL was fully mediated and therefore explainable via fatigue.

Original languageEnglish
Article number751
JournalBrain Sciences
Issue number6
StatePublished - Jun 2021
Externally publishedYes


  • Depression
  • Fatigue
  • Longitudinal
  • Multiple sclerosis
  • Quality of life


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