Evidence map›Paper›PMID 41942462›Full record

ArticleNature communications2026

Downregulated transcription in chromosomal domains of midbrain dopamine neurons linked to schizophrenia.

Swadha Singh, Marina Iskhakova, Tova Y Lambert, Aditi Valada, Neda Shokrian, Viviana Evans, Jaroslav Bendl, Pavan K Auluck, Stefano Marenco, Minghui Wang and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Swadha SinghDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0009-0001-9047-2145
Marina IskhakovaDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Tova Y LambertDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-5005-0087
Aditi ValadaDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Neda ShokrianDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Viviana EvansDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jaroslav BendlDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-9989-2720
Pavan K AuluckHuman Brain Collection Core, National Institute of Mental Health-Intramural Research Program, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-4799-7904
Stefano MarencoHuman Brain Collection Core, National Institute of Mental Health-Intramural Research Program, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2488-2365
Minghui WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-9171-4962
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Gabriel E HoffmanDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-0957-0224
Kiran GirdharDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. kiran.girdhar@mssm.edu.ORCID http://orcid.org/0000-0002-5622-042X
Panos RoussosDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. panagiotis.roussos@mssm.edu.ORCID http://orcid.org/0000-0002-4640-6239
Schahram AkbarianDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. schahram.akbarian@mssm.edu.ORCID http://orcid.org/0000-0001-7700-0891

Funding

Functional genomic resource and integrative model of dopaminergic circuitry associated with psychiatric diseaseU01DA048279 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, BRENNAND, KRISTEN JENNIFER · 2019 to 2023
$3.5M
TRANSCRIPTOME AND EPIGENOME MAPPING IN DOPAMINE NEURONS FROM THE OPIOID EXPOSED HUMAN BRAINR01DA047880 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, BANNON, MICHAEL J · 2019 to 2023
$3.4M
NIDA NIH HHS R01 DA047880NIDA NIH HHS U01 DA048279
6 · The paper itself

Abstract

Ventral midbrain dopaminergic neurons are a key cell type for schizophrenia pathophysiology but information about cell type-specific genomic dysregulation in diseased brains is missing. We generated a unique midbrain functional genomics resource with 97 RNA-seq and 34 Hi-C chromosomal contact libraries for Nurr1 + /NeuN+ dopaminergic and their surrounding Nurr1-/NeuN- nuclei, collected from donors diagnosed with schizophrenia (SCZ), bipolar disorder (BD) and compared to neurotypical controls. Among the 954 dopamine neuron genes specifically dysregulated in SCZ, 331 were downregulated, with selective enrichment for risk-associated synaptic plasticity and neuronal connectivity pathways and embedded within dopamine neuron-specific topologically associated chromosomal domains (TAD). Transcript-resolved analysis revealed 2,350 transcripts with altered expression in SCZ dopamine neurons, affecting key susceptibility genes such as the FOXP1, MAPK10, PCM1 and  NRXN1. Therefore, genomic dysregulation in the ventral midbrain of subjects diagnosed with SCZ selectively affects dopaminergic neurons, and includes a unilateral association of genetic risk with down-, but not upregulated transcription at the sites of highly organized chromosomal domains harboring neuron-specific genes with complex transcriptional architectures.

Indexed as

Dopaminergic NeuronsDown-RegulationMesencephalonSchizophreniaBipolar DisorderFemaleGenetic Predisposition to DiseaseHumansMaleNuclear Receptor Subfamily 4, Group A, Member 2Transcription, GeneticNuclear Receptor Subfamily 4, Group A, Member 2

Identifiers

PMID41942462
PMCPMC13234368

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.