ArticleMultiple sclerosis (Houndmills, Basingstoke, England)2021
Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis.
Article in Multiple sclerosis (Houndmills, Basingstoke, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Polygenicity of Comorbid Depression in Multiple Sclerosis.Neurology · 2023Pooled it
- Shared Genetic Effects and Antagonistic Pleiotropy Between Multiple Sclerosis and Common Cancers.Annals of clinical and translational neurology · 2026Article
- Depression Polygenicity and Disease Activity and Disability Worsening in Multiple Sclerosis.Annals of neurology · 2025Article
- Understanding Depression in People Living with Multiple Sclerosis: A Narrative Review of Recent Literature.Neurology and therapy · 2025Review
- Evidence of symptom specificity for depression in multiple sclerosis: A two sample Mendelian randomization study.Multiple sclerosis and related disorders · 2024Article
- Depression and anxiety in multiple sclerosis. Review of a fatal combination.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Mendelian randomization studies of depression: evidence, opportunities, and challenges.Annals of general psychiatry · 2023Review
- Psychiatric Comorbidity During the Prodromal Period in Patients With Multiple Sclerosis.Neurology · 2023Article
- Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2023Article
- The Barancik lecture: Comorbidity in multiple sclerosis-Looking backward, looking forward.Multiple sclerosis (Houndmills, Basingstoke, England) · 2023Article
- A metabolome-wide Mendelian randomization study prioritizes potential causal circulating metabolites for multiple sclerosis.Journal of neuroimmunology · 2023Article
- Etiology, effects and management of comorbidities in multiple sclerosis: recent advances.Frontiers in immunology · 2023Review
- Depressive symptom trajectories and polygenic risk scores in individuals with an immune-mediated inflammatory disease.General hospital psychiatryArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundMajor depressive disorder (MDD) is common in multiple sclerosis (MS) and its incidence rises before MS diagnosis. However, the causality and direction of this association remain unclear.
objectiveThe objective is to investigate the bidirectional relationship between MS and MDD using Mendelian randomization (MR).
methodsWe selected genetic instruments associated with risk of MDD (
resultsWe found no effect of genetic liability to MDD on the odds of MS (OR = 1.07/doubling in odds, 95% CI = 0.90-1.28). Similarly, our findings did not support a causal effect of genetic liability to MS on MDD (OR = 1.00/doubling in odds, 95% CI = 0.99-1.01). Despite heterogeneity, sensitivity analyses indicated that bias from pleiotropy was unlikely. Conversely, genetic predisposition toward higher BMI increased the odds of MS (OR = 1.34/SD increase, 95% CI = 1.09-1.65) and MDD (OR = 1.08, 95% CI = 1.01-1.15).
conclusionThis study does not support a causal association between MDD genetic liability and MS susceptibility, and vice versa. Genetic evidence suggesting commonality of obesity to both conditions may partly explain the increased incidence of depression pre-MS diagnosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.