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Evidence of symptom specificity for depression in multiple sclerosis: A two sample Mendelian randomization study.

Authors :
Hu C
Vasileiou ES
Salter A
Marrie RA
Kowalec K
Fitzgerald KC
Source :
Multiple sclerosis and related disorders [Mult Scler Relat Disord] 2024 Nov; Vol. 91, pp. 105866. Date of Electronic Publication: 2024 Sep 06.
Publication Year :
2024

Abstract

Background: Depression is common and phenotypically heterogenous in multiple sclerosis (MS). MS may increase risk of some but not all affective symptoms or certain symptoms may predispose individuals to higher MS risk.<br />Objective: To assess the existence and direction of causality between distinct depressive symptoms and MS using two-sample Mendelian randomization (MR).<br />Methods: Using summary data from genome-wide association studies, we selected genetic instrument variables (IV) for MS (n = 115,776) and IVs for depressive symptoms (average n = 117,713): anhedonia, altered appetite, concentration, depressed mood, fatigue, inadequacy, psychomotor changes, sleeping problems and suicidality. We performed two-sample MR in either direction using inverse-variance models. Sensitivity analyses included weighted-median and MR-Egger regression. Obesity is a known risk factor for MS and depression; we adjusted for body mass index in multivariable-MR.<br />Results: Genetic liability to MS was associated with anhedonia (IVW estimate per 10 <superscript>2</superscript> : 0.69; 95 % CI: 0.24-1.13; p = 0.002), concentration difficulty (0.66; 0.19-1.13; p = 0.006) and psychomotor changes (0.37; 0.08-0.65; p = 0.01). Results were similar in sensitivity analyses. In the opposite direction, we found no evidence of a causal relationship for any affective symptom on MS risk.<br />Conclusions: Genetic susceptibility to MS was associated with anhedonia, concentration, and psychomotor-related symptoms, suggesting a specific phenotype of depression in MS.<br />Competing Interests: Declaration of competing interest The authors report no conflicts of interest.<br /> (Copyright © 2024. Published by Elsevier B.V.)

Details

Language :
English
ISSN :
2211-0356
Volume :
91
Database :
MEDLINE
Journal :
Multiple sclerosis and related disorders
Publication Type :
Academic Journal
Accession number :
39276599
Full Text :
https://doi.org/10.1016/j.msard.2024.105866