Evidence map›Paper›PMID 40772555›Full record

ArticleAnnals of neurology2025

Depression Polygenicity and Disease Activity and Disability Worsening in Multiple Sclerosis.

Ali Manouchehrinia, Kathryn C Fitzgerald, Amber Salter, Ruth Ann Marrie, Lars Alfredsson, Charles N Bernstein, James M Bolton, Gary Cutter, John D Fisk, Lesley A Graff and 15 more

Abstract read
In one paragraph

Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Ali ManouchehriniaCollege of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.ORCID 0000-0003-4857-5762
Kathryn C FitzgeraldDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD.ORCID 0000-0003-3137-0322
Amber SalterDepartment of Neurology, UT Southwestern, Dallas, TX.ORCID 0000-0002-1088-110X
Ruth Ann MarrieDepartment of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Lars AlfredssonDepartment of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden.
Charles N BernsteinDepartment of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
James M BoltonDepartment of Psychiatry, Max Rady College of Medicine Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Gary CutterDepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, AL.
John D FiskDepartment of Medicine, Faculty of Medicine, Dalhousie University, Halifax, Canada.
Lesley A GraffDepartment of Clinical Health Psychology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Carol A HitchonDepartment of Rheumatology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Jan HillertDepartment of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden.
Ingrid KockumDepartment of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden.ORCID 0000-0002-0867-4726
Yi LuDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Fred D LublinDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY.
Kyla McKayDepartment of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden.ORCID 0000-0002-9081-1522
Tomas OlssonDepartment of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden.
Scott PattenDepartment of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Amit PatkiDepartment of Psychiatry, Max Rady College of Medicine Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Hayley RielCollege of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Klementy ShchetynskyDepartment of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden.
Pernilla StridhDepartment of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden.
Hemant K TiwariDepartment of Psychiatry, Max Rady College of Medicine Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Jerry S WolinskyDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX.ORCID 0000-0002-8197-2762
Kaarina KowalecCollege of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.ORCID 0000-0003-3928-9879

Funding

A Trans-Nordic Study of Extreme Major DepressionR01MH123724 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PATRICK F SULLIVAN, Lu Yi · 2020 to 2026
$4.7M
CIHR THC-135234Congressionally Directed Medical Research Programs W81XWH2010566Consortium of Multiple Sclerosis Centres, Pilot GrantNIMH NIH HHS MH123724NIMH NIH HHS R01 MH123724University of Manitoba
6 · The paper itself

Abstract

objectiveA better understanding of factors associated with multiple sclerosis (MS) disease activity and disability is needed. Given the strong link between comorbid depression and MS disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with MS disease activity and disability worsening.

methodsIn this cohort study, we used samples from neurologist-defined adult people with MS (PwMS) followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes. We computed the depression polygenic score (PGS) and tested its association with annualized relapse rate and worsening disability. In the US cohort, we additionally explored the time to relapse, number of enhancing lesions, and confirmed Expanded Disability Status Scale (EDSS) worsening during the study period.

resultsWe included 3,420 relapsing-onset PwMS of European genetic ancestry with a median follow-up of 3 to 5 years. Meta-analyses revealed for each 1-standard deviation increase in the depression PGS, the relapse rate increased (incidence rate ratio: 1.23, 95% confidence interval [CI] = 1.01-1.50). In the US cohort, higher depression PGS was associated with protocol-defined relapses (hazard ratio [HR] = 1.58, 95% CI = 1.03-2.43), and time to confirmed EDSS worsening (HR = 1.51, 95% CI = 1.03-2.22) with this effect largely direct.

interpretationMeta-analyses showed a higher depression genetic burden was associated with increased MS disease activity. In the US clinical trial cohort only, we found a significant association between higher depression PGS and time to relapse and confirmed EDSS worsening. These findings may provide insights into MS disease activity and disability worsening. ANN NEUROL 2025;98:1057-1069.

Indexed as

DepressionMultifactorial InheritanceMultiple SclerosisAdultCanadaCohort StudiesDisability EvaluationDisease ProgressionFemaleHumansMaleMiddle AgedPersons with Disabilities

Identifiers

PMID40772555
PMCPMC12577672

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.