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Diagnosis of depression in multiple sclerosis is predicted by frontal–parietal white matter tract disruption

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Abstract

Background

Persons with multiple sclerosis (PwMS) are at an elevated risk of depression. Decreased Conscientiousness may affect patient outcomes in PwMS. Low Conscientiousness has a strong correlation with depression. Previous work has also reported that white matter (WM) tract disruption in frontal–parietal networks explains reduced Conscientiousness in PwMS.

Objective

We hypothesized that Conscientiousness-associated WM tract disruption predicts new-onset depression over 5 years in PwMS and evaluated this by assessing the predictive power of mean Conscientiousness associated frontal–parietal network (CFPN) disruption in PwMS for clinically diagnosed depression over 5 years.

Methods

This longitudinal retrospective analysis included 53 PwMS who were not previously diagnosed as depressed. All participants underwent structural MRI. Medical records were reviewed to evaluate diagnosis of depression for these patients over 5 years. WM tract damage between pairs of gray matter regions in the CFPN was measured using diffusion imaging. The relationship between CFPN disruption and depression was analyzed using logistic regression.

Results

Participants with MS had a mean age of 46.0 years (SD = 11.2). 22.6% (n = 12) acquired a diagnosis of clinical depression over the 5-year period. Baseline disruption in the CFPN was a significant predictor (ROC AUC = 61.8%). of new-onset clinical depression, accounting for age, sex, lateral ventricular volume, disease modifying treatment, and lesion volume.

Conclusion

Baseline CFPN disruption is associated with progression to clinical depression over 5 years in PwMS. Development of new WM pathology within this network may be a risk factor for depression.

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Data availability

Anonymized data will be shared by request from any qualified investigator.

Code availability

All custom code complies with field standards and will be shared by request from any qualified investigator.

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Funding

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Author information

Authors and Affiliations

  1. Department of Neurology, Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (SUNY), 100 High St., Buffalo, NY, 14226, USA

    Kira Ashton, Tom A. Fuchs, Devon Oship, Robert Zivadinov, Dejan Jakimovski, Niels Bergsland, Deepa P. Ramasamy, Bianca Weinstock-Guttman & Michael G. Dwyer

  2. Department of Neurology, Jacobs Multiple Sclerosis Center for Treatment and Research, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (SUNY), Buffalo, NY, USA

    Kira Ashton, Tom A. Fuchs, Devon Oship, Caila Vaughn, Bianca Weinstock-Guttman & Ralph H. B. Benedict

  3. Center for Biomedical Imaging, Clinical Translational Science Institute, University at Buffalo, State University of New York (SUNY), Buffalo, NY, USA

    Robert Zivadinov & Michael G. Dwyer

  4. Center for Behavioral Neuroscience, American University, Washington, DC, USA

    Kira Ashton

  5. IRCCS, Fondazione Don Carlo Gnocchi, Milan, Italy

    Niels Bergsland

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  1. Kira Ashton
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Contributions

KA, TF, and MGD contributed to the study conception and design. Material preparation and analysis were performed by KA, TF, DJ, NB, DR, CV, BWG and MGD. Data collection was performed by RZ, DJ, BWG, and RHBB. The first draft of the manuscript was written by KA, and all authors contributed to revising and drafting previous versions of this manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Michael G. Dwyer.

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Conflicts of interest

Ralph H. B. Benedict has received research support from Accorda, Genzyme, Biogen, and Mallinckrodt, and is on the speakers’ bureau for EMD Serono, consults for Abbvie, Biogen, Genentech, Roche, Sanofi, Verasci, and Novartis, and receives royalties for Psychological Assessment Resources. Robert Zivadinov received personal compensation from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi, Claret Medical, IMS Health and Novartis for speaking and consultant fees. He received financial support for research activities from Teva Pharmaceuticals, Genzyme-Sanofi, Novartis, Claret Medical, Intekrin and IMS Health. Michael G Dwyer received personal compensation from Novartis and Claret Medical for speaking and consultant fees. He received financial support for research activities from Novartis. Bianca Weinstock-Guttman received honoraria as a speaker and as a consultant for Biogen Idec, EMD Serono, Novartis and Mallinckrodt. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis. Caila B Vaughn has received personal compensation from Merck/EMD Serono for consultant fees. Tom Fuchs, Kira Ashton, Niels Bergsland, Dejan Jakimovski, Devon Oship, and Deepa Ramasamy have nothing to disclose.

Ethical standard statement

The study protocol was approved by the University and Buffalo Institutional Ethics Review Board, and was therefore performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to participate

All participants’ written informed consent was obtained before participation.

Consent for publication

All participants’ written informed consent was obtained to publish their de-identified data before participation.

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Ashton, K., Fuchs, T.A., Oship, D. et al. Diagnosis of depression in multiple sclerosis is predicted by frontal–parietal white matter tract disruption. J Neurol 268, 169–177 (2021). https://doi.org/10.1007/s00415-020-10110-3

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  • DOI: https://doi.org/10.1007/s00415-020-10110-3

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