Evidence map›Paper›PMID 38519640›Full record

ArticleMolecular psychiatry2024

Genetic contribution to microglial activation in schizophrenia.

Marja Koskuvi, Elina Pörsti, Tristen Hewitt, Noora Räsänen, Ying-Chieh Wu, Kalevi Trontti, Amanda McQuade, Shringaa Kalyanaraman, Ilkka Ojansuu, Olli Vaurio and 12 more

Open access · hybridAbstract readTwin Study
In one paragraph

Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
8.9field-weighted citation impact, top 2% 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

25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.

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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

22 authors at 5 institutions in 3 countries.

Marja KoskuviNeuroscience Center, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-1646-9992
Elina PörstiNeuroscience Center, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-8880-9909
Tristen HewittNeuroscience Center, University of Helsinki, Helsinki, Finland.
Noora RäsänenNeuroscience Center, University of Helsinki, Helsinki, Finland.
Ying-Chieh WuNeuroscience Center, University of Helsinki, Helsinki, Finland.
Kalevi TronttiNeuroscience Center, University of Helsinki, Helsinki, Finland.
Amanda McQuadeDepartment of Neurobiology & Behavior, UC Irvine, Irvine, CA, USA.ORCID 0000-0001-5368-6788
Shringaa KalyanaramanNeuroscience Center, University of Helsinki, Helsinki, Finland.
Ilkka OjansuuDepartment of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.
Olli VaurioDepartment of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.
Tyrone D CannonDepartment of Psychology and Psychiatry, Yale University, New Haven, CT, USA.ORCID 0000-0002-5632-3154
Jouko LönnqvistMental Health Unit, Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
Sebastian ThermanMental Health Unit, Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.ORCID 0000-0001-9407-4905
Jaana SuvisaariMental Health Unit, Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.ORCID 0000-0001-7167-0990
Jaakko KaprioInstitute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-3716-2455
Mathew Blurton-JonesDepartment of Neurobiology & Behavior, UC Irvine, Irvine, CA, USA.ORCID 0000-0002-7770-7157
Iiris HovattaNeuroscience Center, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-5990-7892
Markku LähteenvuoDepartment of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.ORCID 0000-0002-7244-145X
Taisia RolovaNeuroscience Center, University of Helsinki, Helsinki, Finland.
Šárka LehtonenNeuroscience Center, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-5055-9414
Jari TiihonenNeuroscience Center, University of Helsinki, Helsinki, Finland.
Jari KoistinahoNeuroscience Center, University of Helsinki, Helsinki, Finland. jari.koistinaho@helsinki.fi.ORCID 0000-0001-6559-1153
University of Helsinki · FIUniversity of Eastern Finland · FIFinnish Institute for Health and Welfare · FIUniversity of California, Irvine · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Academy of Finland (Suomen Akatemia) 334525Academy of Finland (Suomen Akatemia) 336823NCATS NIH HHS UL1 TR001863
6 · The paper itself

Abstract

Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Aberrant activation of microglia in SCZ is one of the leading hypotheses for disease pathogenesis, but due to the lack of proper human cell models, the role of microglia in SCZ is not well studied. We used monozygotic twins discordant for SCZ and healthy individuals to generate human induced pluripotent stem cell-derived microglia to assess the transcriptional and functional differences in microglia between healthy controls, affected twins and unaffected twins. The microglia from affected twins had increased expression of several common inflammation-related genes compared to healthy individuals. Microglia from affected twins had also reduced response to interleukin 1 beta (IL1β) treatment, but no significant differences in migration or phagocytotic activity. Ingenuity Pathway Analysis (IPA) showed abnormalities related to extracellular matrix signaling. RNA sequencing predicted downregulation of extracellular matrix structure constituent Gene Ontology (GO) terms and hepatic fibrosis pathway activation that were shared by microglia of both affected and unaffected twins, but the upregulation of major histocompatibility complex (MHC) class II receptors was observed only in affected twin microglia. Also, the microglia of affected twins had heterogeneous response to clozapine, minocycline, and sulforaphane treatments. Overall, despite the increased expression of inflammatory genes, we observed no clear functional signs of hyperactivation in microglia from patients with SCZ. We conclude that microglia of the patients with SCZ have gene expression aberrations related to inflammation response and extracellular matrix without contributing to increased microglial activation.

Indexed as

MicrogliaSchizophreniaTwins, MonozygoticAdultFemaleHumansInduced Pluripotent Stem CellsInflammationInterleukin-1betaIsothiocyanatesMaleMiddle AgedSulfoxidesInterleukin-1betaIsothiocyanatessulforaphaneSulfoxides

Identifiers

PMID38519640
PMCPMC11420079
OpenAlexW4393088065

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.