Mapping the relationship of white matter lesions to depression in multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects nearly one million people in the United States. Up to 50% of patients with MS experience depression. To investigate how white matter network disruption is related to depression in MS. Retrospective case-control study of participants who received research-quality 3-tesla neuroimaging as part of MS clinical care from 2010-2018. Analyses were performed from May 1 to September 30, 2022. Single-center academic medical specialty MS clinic. Participants with MS were identified via the electronic health record (EHR). All participants were diagnosed by an MS specialist and completed research-quality MRI at 3T. After excluding participants with poor image quality, 783 were included. Inclusion in the depression group ( Depression diagnosis. We first evaluated if lesions were preferentially located within the depression network compared to other brain regions. Next, we examined if MS+Depression patients had greater lesion burden, and if this was driven by lesions specifically in the depression network. Outcome measures were the burden of lesions (e.g., impacted fascicles) within a network and across the brain. Secondary measures included between-diagnosis lesion burden, stratified by brain network. Linear mixed-effects models were employed. Three hundred-eighty participants met inclusion criteria, (232 MS+Depression: age[SD]=49[12], %females=86; 148 MS-Depression: age[SD]=47[13], %females=79). MS lesions preferentially affected fascicles within versus outside the depression network (β=0.09, 95% CI=0.08-0.10, P<0.001). MS+Depression had more white matter lesion burden (β=0.06, 95% CI=0.01-0.10, P=0.015); this was driven by lesions within the depression network (β=0.02, 95% CI 0.003-0.040, P=0.020). We provide new evidence supporting a relationship between white matter lesions and depression in MS. MS lesions disproportionately impacted fascicles in the depression network. MS+Depression had more disease than MS-Depression, which was driven by disease within the depression network. Future studies relating lesion location to personalized depression interventions are warranted.

Déclaration de conflit d'intérêts

Conflict of Interest Disclosures: Dr. Baller reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr. Shinohara reported receiving grants from the NIH and the Multiple Sclerosis Society during the conduct of the study. Dr. Shinohara receives consulting income from Octave Bioscience, and compensation for scientific reviewing from the American Medical Association. Dr. Satterthwaite reported receiving grants from the NIH during the conduct of the study.