Evidence map›Paper›PMID 41461239›Full record

ArticleJournal of affective disorders2026

Data-driven symptom dimensions reveal familial patterns in bipolar disorder.

Katie Scott, Claire O'Donovan, Sandra Meier, Barbara Pavlova, Dean F MacKinnon, James B Potash, Thomas G Schulze, Jennifer Judy, Peter P Zandi, NIMH Genetics Initiative Bipolar Disorder Consortium and 4 more

Abstract read
In one paragraph

Article in Journal of affective disorders, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Katie ScottDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada; Nova Scotia Health, Halifax, NS, Canada. Electronic address: katiescott@dal.ca.
Claire O'DonovanDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Sandra MeierDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Barbara PavlovaDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada; Nova Scotia Health, Halifax, NS, Canada.
Dean F MacKinnonDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
James B PotashDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Thomas G SchulzeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA; Department of Psychiatry and Behavioral Sciences, Norton College of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA; Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich, Munich, Germany.
Jennifer JudyDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Peter P ZandiDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
NIMH Genetics Initiative Bipolar Disorder Consortium
Paul GrofMood Disorders Centre of Ottawa, Ottawa, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Francis J McMahonNational Institute of Mental Health, Bethesda, MD, USA.
Abraham NunesDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada; Faculty of Computer Science, Dalhousie University, Halifax, NS, Canada.
Martin AldaDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada; National Institute of Mental Health, Klecany, Czech Republic.

Funding

Identification of Genes Involved in Major Mood DisordersZIAMH002843 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI MCMAHON, FRANCIS J · 2009 to 2025
$24.5M
Intramural NIH HHS ZIA MH002843
6 · The paper itself

Abstract

backgroundBipolar disorder (BD) is a highly heritable psychiatric illness whose clinical and genetic heterogeneity complicates efforts to identify biologically-relevant subtypes. Traditional categorical approaches often fail to capture the multidimensional nature of BD symptomatology. This study aimed to evaluate whether data-driven dimensions show familial aggregation, suggesting potential genetic underpinnings.

methodsUsing two independent cohorts: a primary sample from Halifax (N = 368) and a replication sample from the NIMH Genetics Initiative Bipolar Disorder Consortium (N = 1356), latent dimensions were derived from 21 clinical variables with principal component analysis (PCA). The similarity of relatives in the PCA-derived space was quantified and compared to their similarity with unrelated BD subjects. Mixed-effects models assessed whether familial similarity on latent dimensions increased with degree of relatedness.

resultsAcross both cohorts, the first two principal components (PCs; i.e., mood episode frequency and age of illness onset) were consistent. Overall clinical phenotype was more similar among relatives than among unrelated cases (Halifax: β = 0.316, p = 0.025; NIMH: β = 0.406, p < 0.001; Combined: β = 0.388, p < 0.001). PC 2 (onset) showed significant familial similarity in both cohorts, and PC 1 (episode frequency) showed similarity in the NIMH sample.

conclusionsThese findings suggest that latent clinical dimensions, especially those reflecting mood episode recurrence and age of onset, aggregate within families and may reflect underlying genetic liability in BD. Dimensional, data-driven phenotypes could provide more genetically informative traits than traditional diagnostic subtypes and offer promising targets for future genetic and neurobiological research.

Indexed as

Bipolar DisorderFamilyAdultAge of OnsetCohort StudiesFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedPhenotypePrincipal Component AnalysisBipolar disorderDimensionalFamily studyHeterogeneityPhenotypePrincipal component analysis

Identifiers

PMID41461239
PMCPMC13343236

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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.