Evidence map›Paper›PMID 34291628›Full record

ArticleJournal of psychiatry & neuroscience : JPN2021

Genetic risk for bipolar disorder and schizophrenia predicts structure and function of the ventromedial prefrontal cortex.

Christoph Abé, Predrag Petrovic, William Ossler, William H Thompson, Benny Liberg, Jie Song, Sarah E Bergen, Carl M Sellgren, Peter Fransson, Martin Ingvar and 1 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of psychiatry & neuroscience : JPN, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 2 pooled it
2.1field-weighted citation impact, top 13% of its field
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

13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.

  1. Vaccination and clozapine use: a systematic review and an analysis of the VAERS database.European archives of psychiatry and clinical neuroscience · 2025
    Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Resolving the Delusion Paradox.Schizophrenia bulletin · 2023
    Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
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

11 authors at 4 institutions in 2 countries.

Christoph AbéFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
Predrag PetrovicFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
William OsslerFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
William H ThompsonFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
Benny LibergFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
Jie SongFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
Sarah E BergenFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
Carl M SellgrenFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
Peter FranssonFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
Martin IngvarFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
Mikael LandénFrom the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
University of Gothenburg · SEStanford University · USKarolinska University Hospital · SEKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBipolar disorder is highly heritable and polygenic. The polygenic risk for bipolar disorder overlaps with that of schizophrenia, and polygenic scores are normally distributed in the population. Bipolar disorder has been associated with structural brain abnormalities, but it is unknown how these are linked to genetic risk factors for psychotic disorders.

methodsWe tested whether polygenic risk scores for bipolar disorder and schizophrenia predict structural brain alterations in 98 patients with bipolar disorder and 81 healthy controls. We derived brain cortical thickness, surface area and volume from structural MRI scans. In post-hoc analyses, we correlated polygenic risk with functional hub strength, derived from resting-state functional MRI and brain connectomics.

resultsHigher polygenic risk scores for both bipolar disorder and schizophrenia were associated with a thinner ventromedial prefrontal cortex (vmPFC). We found these associations in the combined group, and separately in patients and drug-naive controls. Polygenic risk for bipolar disorder was correlated with the functional hub strength of the vmPFC within the default mode network. LIMITATIONS: Polygenic risk is a cumulative measure of genomic burden. Detailed genetic mechanisms underlying brain alterations and their cognitive consequences still need to be determined.

conclusionOur multimodal neuroimaging study linked genomic burden and brain endophenotype by demonstrating an association between polygenic risk scores for bipolar disorder and schizophrenia and the structure and function of the vmPFC. Our findings suggest that genetic factors might confer risk for psychotic disorders by influencing the integrity of the vmPFC, a brain region involved in self-referential processes and emotional regulation. Our study may also provide an imaging-genetics vulnerability marker that can be used to help identify individuals at risk for developing bipolar disorder.

Indexed as

Genetic Predisposition to DiseaseAgingBipolar DisorderFemaleHumansMagnetic Resonance ImagingMaleMultifactorial InheritancePrefrontal CortexRisk FactorsSchizophrenia

Identifiers

PMID34291628
PMCPMC8519489
OpenAlexW3185117285

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.