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

Autor:	Baller EB; Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Philadelphia, PA USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA USA., Sweeney EM; Penn Statistics in Imaging and Visualization Center (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA USA., Cieslak MC; Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Philadelphia, PA USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA USA., Robert-Fitzgerald T; Penn Statistics in Imaging and Visualization Center (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA USA., Covitz SC; Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Philadelphia, PA USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA USA., Martin ML; Penn Statistics in Imaging and Visualization Center (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA USA., Schindler MK; Department of Neurology, University of Pennsylvania, Philadelphia, PA USA.; Center for Neuroinflammation and Neurotherapeutics, University of Pennsylvania, Philadelphia, PA USA., Bar-Or A; Department of Neurology, University of Pennsylvania, Philadelphia, PA USA.; Center for Neuroinflammation and Neurotherapeutics, University of Pennsylvania, Philadelphia, PA USA., Elahi A; Department of Information Services, University of Pennsylvania, Philadelphia, PA USA., Larsen BS; Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Philadelphia, PA USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA USA., Manning AR; Penn Statistics in Imaging and Visualization Center (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA USA., Markowitz CE; Department of Neurology, University of Pennsylvania, Philadelphia, PA USA.; Center for Neuroinflammation and Neurotherapeutics, University of Pennsylvania, Philadelphia, PA USA., Perrone CM; Department of Neurology, University of Pennsylvania, Philadelphia, PA USA.; Center for Neuroinflammation and Neurotherapeutics, University of Pennsylvania, Philadelphia, PA USA., Rautman V; Department of Information Services, University of Pennsylvania, Philadelphia, PA USA., Seitz MM; Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Philadelphia, PA USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA USA.; Penn Statistics in Imaging and Visualization Center (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA USA., Detre JA; Department of Neurology, University of Pennsylvania, Philadelphia, PA USA., Fox MD; Center for Brain Circuit Therapeutics, Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School., Shinohara RT; Penn Statistics in Imaging and Visualization Center (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA USA.; Center for Biomedical Image Computing and Analytics (CBICA), University of Pennsylvania, Philadelphia, PA USA., Satterthwaite TD; Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Philadelphia, PA USA.; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA USA.; Center for Biomedical Image Computing and Analytics (CBICA), University of Pennsylvania, Philadelphia, PA USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Jun 12. Date of Electronic Publication: 2023 Jun 12.
DOI:	10.1101/2023.06.09.23291080
Abstrakt:	Importance: 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. Objective: To investigate how white matter network disruption is related to depression in MS. Design: 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. Setting: Single-center academic medical specialty MS clinic. Participants: 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 ( MS+Depression ) required either: 1) ICD-10 depression diagnosis (F32-F34.*); 2) prescription of antidepressant medication; or 3) screening positive via Patient Health Questionnaire-2 (PHQ-2) or -9 (PHQ-9). Age- and sex-matched nondepressed comparators ( MS - Depression ) included persons with no depression diagnosis, no psychiatric medications, and were asymptomatic on PHQ-2/9. Exposure: Depression diagnosis. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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. Competing Interests: 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.
Databáze:	MEDLINE
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