Longitudinal Relationships Between Moderate and Vigorous Physical Activity, Fatigue and Depression in Pediatric MS

Background:   Cross-sectional studies of children with demyelinating disorders have reported an association between higher levels of moderate/vigorous physical activity (MVPA) and less fatigue and depression. Longitudinal studies can provide further insight into these relationships.

Objectives: To examine the longitudinal relationship between MVPA, fatigue and depression in youth with MS and monophasic demyelinating conditions (mono-ADS).

Methods: Serial standardized fatigue, depression, and physical activity (PA) questionnaires were collected from consecutive MS and mono-ADS youth attending the Pediatric MS and Neuroinflammatory Disorders Clinic at The Hospital for Sick Children, Toronto, Canada (2013-2016). We calculated self-reported PA levels using metabolic equivalents (METS).  We used mixed generalized linear models to explore the associations of MVPA with fatigue over time while controlling for age and time from disease onset, sex, relapse rate, depression, and EDSS. We also modeled depression as a categorical term to test the role of clinically significant depression on fatigue.  Depression was also modeled as the dependent variable in order to further test the relationship between MVPA, fatigue and depression.

Results: 180 patients were included (49=MS, 131=mono-ADS (77M, 103F)).  We found a trajectory of increased fatigue based on age of onset in both mono-ADS and MS (estimate 0.98 point increase/year, p<0.0001) and increased fatigue with disease duration in both groups (estimate 0.96 point increase/year, p=0.0007).    Participation in MVPA did not have an effect on fatigue when depression was included in the model.  Over time, youth who reported clinically significant depression at any time point had increased fatigue (estimate 13.1, p< 0.0001) in comparison to non-depressed youth. Youth with MS also had higher depression scores (estimate=7.3, p< 0.0002) than mono-ADS. In our model, for every MET increase in MVPA there was an associated decrease in depression score of -0.09 (p= 0.0004) in MS youth.

Conclusions: In youth with MS, the effect of MVPA on fatigue appeared to be mediated by depression. Small increases in MVPA (1 MET) were associated with improvements in depression in youth with MS through time, which may, in turn, contribute to reduced fatigue. Our results may serve as the backdrop for planning future interventions to improve outcomes in youth with MS.