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Microstructural changes precede depression in patients with relapsing-remitting Multiple Sclerosis.

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BACKGROUND: Multiple Sclerosis lesions in the brain and spinal cord can lead to different symptoms, including cognitive and mood changes. In this study we explore the temporal relationship between early microstructural changes in subcortical volumes and cognitive and emotional function in a longitudinal cohort study of patients with relapsing-remitting Multiple Sclerosis. METHODS: In vivo imaging in forty-six patients with relapsing-remitting Multiple Sclerosis was performed annually over 3 years magnetic resonance imaging. Microstructural changes were estimated in subcortical structures using the free water fraction, a diffusion-based MRI metric. In parallel, patients were assessed with the Hospital Anxiety and Depression Scale amongst other tests. Predictive structural equation modeling was set up to further explore the relationship between imaging and the assessment scores. In a general linear model analysis, the cohort was split into patients with higher and lower depression scores. RESULTS: Nearly all subcortical diffusion microstructure estimates at the baseline visit correlate with the depression score at the 2 years follow-up. The predictive nature of baseline free water estimates and depression subscores after 2 years are confirmed in the predictive structural equation modeling analysis with the thalamus showing the greatest effect size. The general linear model analysis shows patterns of MRI free water differences in the thalamus and amygdala/hippocampus area between participants with high and low depression score. CONCLUSIONS: Our data suggests a relationship between higher levels of free-water in the subcortical structures in an early stage of Multiple Sclerosis and depression symptoms at a later stage of the disease.


Acknowledgements: The authors would like to thank the MS patients for participation in the study, and express their thanks to the Health Authorities of Western Norway for funding of the project. We are grateful to Nuno Pedrosa de Barros from Icometrix for providing the lesion analyses and to scientists Hauke Bartsch and Erling Andersen, Haukeland University Hospital, for their involvement in MRI data collection, handling and storage. We are thankful to the team of neuroradiologists at the Department of Radiology, Haukeland University Hospital, for MR image reading and reporting. We are obliged to MS nurses Anne-Britt Rundhovde Skår and Randi C. Haugstad at the Norwegian MS Competence Center, Haukeland University Hospital, for their invaluable contribution to the study, and to health secretary Angunn Solberg at the outpatient clinic at the Department of Neurology, Haukeland University Hospital, for her contribution to logistics. MMIV is jointly hosted by Haukeland University Hospital and University of Bergen and supported as a centre by grants from the Trond Mohn Foundation. Neuro-SysMed is jointly hosted by Haukeland University Hospital and University of Bergen and supported as a centre for Clinical Treatment Research (FKB) by grants from The Research Council of Norway, project number 288164. Ellen Skorve has received majority of funding through PhD-scholarship from the Health Authorities of Western Norway (3-year fellowship). Additional financial support for the MRI investigation study was provided by Dr. Niels Vilhelm Henrichsen and wife Anna Henrichsens Legacy Fund.

Funder: Helse Vest (Western Norway Regional Health Authority); doi:

Funder: Trond Mohn Foundation: Dr. Niels Vilhelm Henrichsen and wife Anna Henrichsens Legacy Fund:øknadsskjema Henrichsens legat.pdf


5202 Biological Psychology, 52 Psychology, Brain Disorders, Mental Health, Neurodegenerative, Depression, Behavioral and Social Science, Neurosciences, Biomedical Imaging, Autoimmune Disease, Clinical Research, Multiple Sclerosis, Neurological, Mental health

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Commun Med (Lond)

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Springer Science and Business Media LLC
Norges Forskningsråd (Research Council of Norway) (288164)