Evidence map›Paper›PMID 39889373›Full record

ArticleEBioMedicine2025

Genetic insights into psychotic major depressive disorder: bridging the mood-psychotic disorder spectrum.

Thuy-Dung Nguyen, Joeri J Meijsen, Robert Sigström, Ralf Kuja-Halkola, Ying Xiong, Arvid Harder, Kaarina Kowalec, Joëlle A Pasman, Carolina Scarpa, Elin Hörbeck and 15 more

Abstract read
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Antidepressant Augmentation of Antipsychotic Treatment in Schizophrenia: A Narrative Review.Medical science monitor : international medical journal of experimental and clinical research · 2026
    Review
  3. Article
  4. 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.

Thuy-Dung NguyenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
Joeri J MeijsenInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Robert SigströmDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Affective Clinic, Sahlgrenska University Hopsital, Gothenburg, Sweden.
Ralf Kuja-HalkolaDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ying XiongDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Arvid HarderDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Kaarina KowalecDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; College of Pharmacy, University of Manitoba, Winnipeg, Canada.
Joëlle A PasmanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands.
Carolina ScarpaDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Psychiatry "ASST Fatebenefratelli-Sacco", University of Milan, Milan, Italy.
Elin HörbeckDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Lina JonssonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Sara HäggDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Niamh MullinsDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., New York, USA.
Kevin S O'ConnellNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Christina DalmanDepartment of Global Public Health, Karolinska Institutet, Stockholm, Sweden; Center for Epidemiology and Community Medicine, Stockholm, Sweden.
Dorte HeleniusInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Richard ZetterbergInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Henrik LarssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.
Paul LichtensteinDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ole A AndreassenNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo and Oslo University Hospital, Oslo, Norway.
Thomas WergeInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Alfonso BuilInstitute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Mikael LandénDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Patrick F SullivanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, USA.
Yi LuDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden. Electronic address: lu.yi@ki.se.

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
NIMH NIH HHS R01 MH123724
6 · The paper itself

Abstract

backgroundPsychotic major depressive disorder (MDD), a subtype of MDD characterised by psychotic symptoms that occur exclusively during mood episode, is clinically significant yet underexplored genetically due to its rarity. This study comprehensively examines the genetic basis of psychotic MDD and elucidates its position within the mood-psychotic spectrum.

methodsThis population-based cohort study used Swedish and Danish registry data for over 5.1 M individuals born between 1958 and 1993/1996. Specialist-diagnosed psychotic MDD was defined using ICD-10 sub-codes of MDD, F32.2/F32.3. We estimated familial aggregation/coaggregation using generalised estimating equations, heritability and genetic correlations using structural equation modelling. We also analysed ∼30,000 genotyped MDD cases from the UK Biobank and a Swedish cohort to explore which polygenic risk score (PRS) may predispose individuals to psychotic MDD.

findingsWith over 10,000 psychotic MDD identified from the two nationwide patient registers, this study highlights the familial aggregation of psychotic MDD, co-aggregation with mood and psychotic disorders, and its stronger genetic correlation with schizophrenia compared to non-psychotic MDD. The familial risks increased with closer biological relatedness, suggesting genetic influence. Pedigree-heritability of psychotic MDD was 30.17% (95% CI 23.53-36.80%). While the genetic correlation between psychotic and non-psychotic MDD was high (0.82, 95% CI 0.73-0.92), the psychotic subgroup showed a higher genetic correlation with schizophrenia than non-psychotic MDD (0.67 vs 0.46, p-value 7.55∗10

interpretationThis study provides evidence for the genetic basis of psychotic MDD, underscoring its unique position bridging the spectrum of mood and psychotic disorders. These findings advance our understanding of the aetiology of psychotic MDD and contribute to the limited body of evidence on this phenotype by utilising large-scale population-based data.

fundingEuropean Research Council; US National Institutes of Mental Health; European Union Horizon 2020 Program; Swedish Research Council; Research Council of Norway; Swedish Foundation for Strategic Research; Hjärnfonden.

Indexed as

Genetic Predisposition to DiseaseMajor Depressive DisorderPsychotic DisordersAdultAgedCohort StudiesDenmarkFemaleGenotypeHumansMaleMiddle AgedMultifactorial InheritancePedigreeRegistriesRisk FactorsEpidemiologyGeneticPsychotic disordersPsychotic major depressive disorder

Identifiers

PMID39889373
PMCPMC11830301

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.