Related Experiment Video
Updated: Jun 13, 2025
Author Spotlight: Creating a Versatile Experimental Autoimmune Encephalomyelitis Model Relevant for Both Male and Female Mice
Published on: October 13, 2023
Evidence of symptom specificity for depression in multiple sclerosis: A two sample Mendelian randomization study
Chen Hu1, Eleni S Vasileiou1, Amber Salter2
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
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.
Objective:
To assess the existence and direction of causality between distinct depressive symptoms and MS using two-sample Mendelian randomization (MR).
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.
Results:
Genetic liability to MS was associated with anhedonia (IVW estimate per 102: 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.
Conclusions:
Genetic susceptibility to MS was associated with anhedonia, concentration, and psychomotor-related symptoms, suggesting a specific phenotype of depression in MS.
Insights
Genetic susceptibility to multiple sclerosis (MS) is linked to specific depression symptoms like anhedonia and concentration issues. This study used Mendelian randomization to explore the causal link between MS and various depressive symptoms.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Depression is a common and varied condition in multiple sclerosis (MS).
- MS may influence the risk of certain affective symptoms, or conversely, some symptoms might increase MS risk.
Purpose of the Study:
- To investigate the causal relationship between distinct depressive symptoms and MS.
- To determine the directionality of causality using two-sample Mendelian randomization (MR).
Main Methods:
- Utilized genome-wide association study data for MS (n=115,776) and depressive symptoms (n=117,713).
- Assessed nine depressive symptoms: anhedonia, altered appetite, concentration, depressed mood, fatigue, inadequacy, psychomotor changes, sleeping problems, and suicidality.
- Employed two-sample MR with inverse-variance models and sensitivity analyses, adjusting for body mass index in multivariable-MR.
Main Results:
- Found genetic liability to MS associated with anhedonia, concentration difficulty, and psychomotor changes.
- Sensitivity analyses confirmed these associations.
- No evidence of a causal relationship was found for any depressive symptom influencing MS risk.
Conclusions:
- Genetic susceptibility to MS is specifically associated with anhedonia, concentration difficulties, and psychomotor changes.
- These findings suggest a distinct depressive symptom phenotype in individuals with MS.
Related Concept Videos
01:27Depressive Disorders: Etiology
Biological Factors in Depression
Biological predispositions significantly influence the risk of developing depressive disorders. Genetic studies highlight the role of variations in the serotonin transporter...
01:27Depressive Disorders: MDD and Dysthymia
01:23Antidepressant Drugs: MAOIs and Other Agents