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MS Fatigue Consistently Linked With Depressive Symptoms

The study covered in this summary was published in as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Fatigue imposes a significant burden on patients with relapsing-remitting multiple sclerosis (MS), even early in the disease course.

  • Subjective fatigue severity is consistently associated with depressive symptoms in this population.

  • Specifically, subjective fatigue severity is linked with distinct depressive symptoms, such as anhedonia and subjective concentration deficits.

Why This Matters

  • Treatments for fatigue in patients with MS have limited efficacy, which reflects a limited understanding of and lack of biomarkers for this symptom.

  • In patients with MS, it can be difficult to distinguish subjective fatigue from other phenomena, such as depression and physical fatigability.

  • Factors such as disability, obesity, depression, and sleep disturbance have been linked with fatigue in some studies, but the link has not been replicated in subsequent studies.

  • A multivariate analysis could improve understanding of the relationships between these variables and the mechanisms underlying fatigue in MS.

Study Design

  • The researchers examined participants in FutureMS, a nationally representative cohort of patients with newly diagnosed relapsing-remitting MS in Scotland, United Kingdom.

  • They selected patients for whom data had been collected at baseline and 12-month follow-up.

  • Among the clinical and patient-reported variables that they selected were fatigue, physical disability, upper limb dexterity, walking speed, body mass index, information processing speed, working memory, anxiety, depression, and sleep.

  • Imaging variables included white matter hyperintensities, cortical gray matter volume, basal ganglia volume, and thalamus volume.

Key Results

  • The investigators included 440 patients (median age, 36 years; median disease duration, 1.8 years) in their analysis.

  • The population’s median level of fatigue, as measured by the Fatigue Severity Score (FSS), was mild to moderate (FSS, 35).

  • Approximately half of participants reported significant fatigue (FSS ≥36).

  • Fatigue severity did not differ significantly between baseline and month 12.

  • Bivariate analysis indicated that fatigue severity was significantly correlated with all measures of physical disability, anxiety, depression, cognitive performance (specifically, processing speed and memory or attention), and sleep quality.

  • Fatigue severity was not correlated with structural brain imaging variables in bivariate analysis.

  • Network analysis indicated that fatigue was strongly correlated with depression and disability, as measured by the Expanded Disability Status Scale.

  • When the researchers controlled the data for “tiredness” in the measure of depression, the depressive symptoms of anhedonia, subjective concentration deficits, subjectively altered speed of movement, and appetite remained associated with fatigue.

  • Fatigue was not associated with objective cognitive performance, white matter lesion volume, or gray matter volumes.

  • Results were consistent at baseline and month 12.

  • The researchers identified depression as the most important variable in the network analysis.


  • The FSS may be biased toward the physical aspects of fatigue.

  • Conclusions about causality cannot be made based on the cross-sectional analyses included in this study.

  • Not all variables that could be linked with fatigue, such as pain, were included in the analysis.

Study Disclosures

  • The authors reported no conflicts of interest.

This is a summary of a preprint research study, “Data-Driven Analysis Shows Robust Links Between Fatigue and Depression in Early Multiple Sclerosis,” written by Yuan-Ting Chang from University of Edinburgh on medRxiv provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

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