Factors associated with depressive mood at the onset of multiple sclerosis - an analysis of 781 patients of the German NationMS cohort

Anke Salmen; Robert Hoepner; Vinzenz Fleischer; Milena Heldt; Barbara Gisevius; Jeremias Motte; Klemens Ruprecht; Ruth Schneider; Anna Lena Fisse; Thomas Grüter; Carsten Lukas; Achim Berthele; Katrin Giglhuber; Martina Flaskamp; Mark Mühlau; Jan Kirschke; Stefan Bittner; Sergiu Groppa; Felix Lüssi; Antonios Bayas; Sven Meuth; Cristoph Heesen; Corinna Trebst; Brigitte Wildemann; Florian Then Bergh; Gisela Antony; Tania Kümpfel; Friedemann Paul; Sandra Nischwitz; Hayrettin Tumani; Uwe Zettl; Bernhard Hemmer; Heinz Wiendl; Frauke Zipp; Ralf Gold

doi:10.1177/17562864231197309

Factors associated with depressive mood at the onset of multiple sclerosis - an analysis of 781 patients of the German NationMS cohort

Ther Adv Neurol Disord. 2023 Sep 8:16:17562864231197309. doi: 10.1177/17562864231197309. eCollection 2023.

Authors

Anke Salmen^{1

2}, Robert Hoepner², Vinzenz Fleischer³, Milena Heldt³, Barbara Gisevius⁴, Jeremias Motte⁴, Klemens Ruprecht^{5

6}, Ruth Schneider^{4

7}, Anna Lena Fisse⁴, Thomas Grüter⁴, Carsten Lukas^{4

7}, Achim Berthele⁸, Katrin Giglhuber⁸, Martina Flaskamp⁸, Mark Mühlau⁸, Jan Kirschke⁹, Stefan Bittner³, Sergiu Groppa³, Felix Lüssi³, Antonios Bayas¹⁰, Sven Meuth¹¹, Cristoph Heesen¹², Corinna Trebst¹³, Brigitte Wildemann¹⁴, Florian Then Bergh¹⁵, Gisela Antony¹⁶, Tania Kümpfel¹⁷, Friedemann Paul^{5

6}, Sandra Nischwitz¹⁸, Hayrettin Tumani¹⁹, Uwe Zettl²⁰, Bernhard Hemmer^{8

21}, Heinz Wiendl²², Frauke Zipp³, Ralf Gold⁴

Affiliations

¹ Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany.
² Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
³ Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
⁴ Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany.
⁵ Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁶ Experimental and Clinical Research Center and NeuroCure Clinical Research Center, MaxDelbrueck Center for Molecular Medicine and Charité Universitätsmedizin Berlin, Berlin, Germany.
⁷ Institute for Neuroradiology, St. Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany.
⁸ Department of Neurology, Klinikum rechtsDer Isar, Technical University of Munich, Munich, Germany.
⁹ Department of Neuroradiology, Klinikum rechtsDer Isar, Technical University of Munich, Munich, Germany.
¹⁰ Department of Neurology, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
¹¹ Department of Neurology, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany.
¹² Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
¹³ Department of Neurology, Hannover Medical School, Hannover, Germany.
¹⁴ Molecular Neuroimmunology Group, Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.
¹⁵ Department of Neurology, University of Leipzig, Leipzig, Germany.
¹⁶ Central Information Office German Competence Network of Multiple Sclerosis, Philipps University Marburg, Marburg, Germany.
¹⁷ Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilian-University Munich, Munich, Germany.
¹⁸ Max Planck Institute of Psychiatry, Munich, Germany.
¹⁹ Department of Neurology, University of Ulm, Ulm, Germany.
²⁰ Department of Neurology, Neuroimmunological Section, University of Rostock, Rostock, Germany.
²¹ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
²² Department of Neurology with Institute of Translational Neurology, Medical Faculty, University Hospital, Münster, Germany.

Abstract

Background: Depression has a major impact on the disease burden of multiple sclerosis (MS). Analyses of overlapping MS and depression risk factors [smoking, vitamin D (25-OH-VD) and Epstein-Barr virus (EBV) infection] and sex, age, disease characteristics and neuroimaging features associated with depressive symptoms in early MS are scarce.

Objectives: To assess an association of MS risk factors with depressive symptoms within the German NationMS cohort.

Design: Cross-sectional analysis within a multicenter observational study.

Methods: Baseline data of n = 781 adults with newly diagnosed clinically isolated syndrome or relapsing-remitting MS qualified for analysis. Global and region-specific magnetic resonance imaging (MRI)-volumetry parameters were available for n = 327 patients. Association of demographic factors, MS characteristics and risk factors [sex, age, smoking, disease course, presence of current relapse, expanded disability status scale (EDSS) score, fatigue (fatigue scale motor cognition), 25-OH-VD serum concentration, EBV nuclear antigen-1 IgG (EBNA1-IgG) serum levels] and depressive symptoms (Beck Depression Inventory-II, BDI-II) was tested as a primary outcome by multivariable linear regression. Non-parametric correlation and group comparison were performed for associations of MRI parameters and depressive symptoms.

Results: Mean age was 34.3 years (95% confidence interval: 33.6-35.0). The female-to-male ratio was 2.3:1. At least minimal depressive symptoms (BDI-II > 8) were present in n = 256 (32.8%), 25-OH-VD deficiency (<20 ng/ml) in n = 398 (51.0%), n = 246 (31.5%) participants were smokers. Presence of current relapse [coefficient (c) = 1.48, p = 0.016], more severe fatigue (c = 0.26, p < 0.0001), lower 25-OH-VD (c = -0.03, p = 0.034) and smoking (c = 0.35, p = 0.008) were associated with higher BDI-II scores. Sex, age, disease course, EDSS, month of visit, EBNA1-IgG levels and brain volumes at baseline were not.

Conclusion: Depressive symptoms need to be assessed in early MS. Patients during relapse seem especially vulnerable to depressive symptoms. Contributing factors such as fatigue, vitamin D deficiency and smoking, could specifically be targeted in future interventions and should be investigated in prospective studies.

Keywords: CIS; MRI; MS; clinically isolated syndrome; cohort study; depression; neuropsychological symptoms; relapse; sex; smoking; vitamin D.