Evidence map›Paper›PMID 41022686›Full record

SynthesisTranslational psychiatry2025

Meta-analysis of the brain transcriptomes of multiple genetic mouse models of schizophrenia highlights dysregulation in striatum and thalamus.

Kira A Perzel Mandell, Sean K Simmons, Ajay Nadig, Zohreh Farsi, Wei-Chao Huang, Sameer Aryal, Min Jee Kwon, Bryan Song, Kira Brenner, Nate Shepard and 5 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Translational psychiatry, 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

15 authors.

Kira A Perzel MandellStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. kperzelm@broadinstitute.org.ORCID http://orcid.org/0000-0001-6262-6904
Sean K SimmonsStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ajay NadigStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9634-2141
Zohreh FarsiStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7274-981X
Wei-Chao HuangStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sameer AryalStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3577-4383
Min Jee KwonStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Bryan SongStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0549-4823
Kira BrennerStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6638-5300
Nate ShepardStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8629-3152
Ally A NicolellaStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Lesley D O'BrienVirginia Commonwealth University, Richmond, VA, USA.ORCID http://orcid.org/0000-0002-5877-3976
Aron H LichtmanVirginia Commonwealth University, Richmond, VA, USA.
Joshua Z LevinStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0170-3598
Morgan ShengStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. msheng@broadinstitute.org.ORCID http://orcid.org/0000-0002-8703-5366

Funding

TRAINING IN THE PHARMACOLOGY OF ABUSED DRUGST32DA007027 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI William L. Dewey · 1985 to 2026
$14.7M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
VCU Center for Drug Addiction ResearchP30DA033934 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI JOLENE J WINDLE · 2014 to 2026
$13.8M
Endocannabinoid Biosynthesis in Inflammation and PainR01DA043571 · NIDA · UNIVERSITY OF VIRGINIA · PI Ku-Lung Hsu · 2017 to 2026
$3.5M
NIDA NIH HHS P30 DA033934NIDA NIH HHS R01 DA043571NIDA NIH HHS T32 DA007027NIGMS NIH HHS T32 GM144273
6 · The paper itself

Abstract

Schizophrenia is a severe mental illness with high heritability, but its underlying mechanisms are poorly understood. We meta-analyzed large-scale brain transcriptomic data from mice harboring individual loss-of-function mutations in seven schizophrenia risk genes (Akap11, Dagla, Gria3, Grin2a, Sp4, Srrm2, Zmym2). While all studied brain regions were affected, the striatum and the thalamus emerged as key brain regions of convergence. Striatum showed downregulation of synapse- and oxidative phosphorylation-related gene sets in all models. In the thalamus, mutants separated into two groups based on transcriptomic phenotype: synapse-related gene sets were upregulated in mutants with only schizophrenia and bipolar association, and were downregulated in mutants that are associated with developmental delay/intellectual disability in addition to schizophrenia. Overall, our meta-analysis reveals convergence and divergence in brain transcriptomic phenotype in these schizophrenia genetic models, supports the involvement of striatal disturbance and synapse dysfunction in schizophrenia, and points to a key role of the thalamus.

Indexed as

Corpus StriatumSchizophreniaThalamusTranscriptomeAnimalsDisease Models, AnimalMice

Identifiers

PMID41022686
PMCPMC12480767

What OpenQuestion holds

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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.