Depression mediates the relationship between fatigue and mental health-related quality of life in multiple sclerosis

Background: Fatigue is among the most prevalent symptoms for people with multiple sclerosis (pwMS) and is significantly detrimental to mental health-related (mental) quality of life (QoL). We examined the role of depression and physical activity as mediators in the fatigue-QoL relationship in pwMS. Methods: Using baseline cross-sectional data from an international cohort of 2,104 pwMS, characteristics of fatigue and mental QoL, measured by Fatigue Severity Scale and MSQOL-54 respectively, were assessed using linear and log-binomial regression. Structural Equation Models (SEM) were used to explore the mediating roles of depression and physical activity between fatigue and mental QoL. Results: The median mental QoL score was 71.9/100. The mean fatigue score was 41.5/63, with 65.6% participants having clinically significant fatigue. In the SEM evaluating depression as a mediator of the fatigue-QoL relationship, mental QoL was 14.72 points lower (95% CI: -16.43 -13.01, pConclusion: Depression accounted for the majority of the fatigue-mental QoL relationship when modelled as a mediator, while physical activity had only a minor role. Our findings may inform the development of treatments for reducing the impacts of fatigue and improving mental QoL in pwMS