Investigating Mood and Cognition in People with Multiple Sclerosis: A Prospective Study Protocol

  1. Elena C. Cooper
  2. Matthew K. Schindler
  3. Amit Bar-Or
  4. Rachel B. Brandstadter
  5. Monica E. Calkins
  6. Ruben C. Gur
  7. Dina A. Jacobs
  8. Clyde E. Markowitz
  9. Tyler M. Moore
  10. Laura R. Naydovich
  11. Christopher M. Perrone
  12. Kosha Ruparel
  13. Bailey C. Spangler
  14. Scott Troyan
  15. Russell T. Shinohara
  16. Theodore D. Satterthwaite
  17. Erica B. Baller
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Abstract

Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects one million people in the United States. Up to 50% of people with MS experience depression, yet the mechanisms of depression in MS remain under-investigated. Studies of medically healthy participants with depression have described associations between white matter variability and depressive symptoms, but frequently exclude participants with medical comorbidities and thus cannot be extrapolated to people with intracranial diseases. White matter lesions are a key pathologic feature of MS and could disrupt pathways involved in depression symptoms. The purpose of this study is to investigate the impact of brain network disruption on depression using MS as a model. We will obtain structured clinical and cognitive assessments from two hundred fifty participants with MS and prospectively evaluate white matter lesion burden as a predictor of depressive symptoms. Ethics approval was obtained from The University of Pennsylvania Institutional Review Board (Protocol #853883). The results of this study will be presented at scientific meetings and conferences and published in peer-reviewed journals.

ARTICLE SUMMARY

Strengths and Limitations of this Study

  • We will use MS as a model to study how white matter disease contributes to both the pathophysiology of depression in MS and to general network mechanisms of depression.

  • We will leverage research-grade 3-tesla (3T) MRIs acquired as part of routine MS care and maximize scalability by using the Method for Inter-Modal Segmentation Analysis (MIMoSA) for automated white matter lesion segmentation.

  • Our study will include participants with medical comorbidities, creating a more representative population and more broadly applicable results.

  • We will obtain detailed clinical and cognitive assessments from each participant to evaluate the inter-relationship of mood symptoms, anxiety symptoms, and cognitive deficits, and relate them to white matter disease.

  • This is a single-center study.

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  1. Version published to 10.1101/2024.10.02.24314787v1 on medRxiv