Evidence map›Paper›PMID 37205394›Full record

ArticlebioRxiv : the preprint server for biology2023

ZBTB7A regulates MDD-specific chromatin signatures and astrocyte-mediated stress vulnerability in orbitofrontal cortex.

Sasha L Fulton, Jaroslav Bendl, Isabel Gameiro-Ros, John F Fullard, Amni Al-Kachak, Ashley E Lepack, Andrew F Stewart, Sumnima Singh, Wolfram C Poller, Ryan M Bastle and 16 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 5 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 6 institutions in 1 country.

Sasha L FultonFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Jaroslav BendlFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Isabel Gameiro-RosFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
John F FullardFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Amni Al-KachakFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Ashley E LepackFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Andrew F StewartFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Sumnima SinghDepartment of Cardiology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Wolfram C PollerDepartment of Cardiology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Ryan M BastleFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Mads E HaubergCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Amanda K FakiraFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Min ChenFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Romain Durand-de CuttoliFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Flurin CathomasFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Aarthi RamakrishnanFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Kelly GleasonDepartment of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA.
Li ShenFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Carol A TammingaDepartment of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA.
Ana MilosevicLaboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York, USA.
Scott J RussoFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Filip SwirskiDepartment of Cardiology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Robert D BlitzerDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Paul A SlesingerFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Panos RoussosFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Ian MazeFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Allen Institute for Brain Science · USCardiovascular Institute of the South · USIcahn School of Medicine at Mount Sinai · USSouthwestern Medical Center · USNathan Kline Institute for Psychiatric Research · USRockefeller University · US

Funding

REPRESSIVE HISTONE AND DNA METHYLATION IN RODENT DEPRESSION MODELSP50MH096890 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ALLIS, CHARLES DAVID · 2012 to 2021
$20.2M
Molecular Profiling of SchizophreniaR01MH110921 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHESS, ANDREW J, ROUSSOS, PANAGIOTIS · 2016 to 2020
$6.9M
The 3D genome in transcriptional regulation across the postnatal life span, with implications for schizophrenia and bipolar disorderU01MH116442 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, DRACHEVA, STELLA · 2018 to 2022
$5.9M
Molecular studies of neural histone monoaminylation in normal and aberrant brain plasticityR01MH116900 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ian S. Maze · 2019 to 2026
$4.7M
Risk genetic variants and cis regulation of gene expression in Bipolar DisorderR01MH109677 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2016 to 2020
$4.6M
Defining the molecular basis of autism caused by inherited null mutations in BAF53BF31MH116588 · NIMH · STANFORD UNIVERSITY · PI WENDERSKI, WENDY · 2018 to 2020
$92k
Characterizing effects of OFC astrocyte plasticity in inflammation response and stress vulnerability with single-cell resolutionF99NS125774 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FULTON, SASHA · 2021 to 2021
$45k
NIMH NIH HHS F31 MH116588NIMH NIH HHS P50 MH096890NIMH NIH HHS R01 MH109677NIMH NIH HHS R01 MH110921NIMH NIH HHS R01 MH116900NIMH NIH HHS U01 MH116442NINDS NIH HHS F99 NS125774
6 · The paper itself

Abstract

Hyperexcitability in the orbitofrontal cortex (OFC) is a key clinical feature of anhedonic domains of Major Depressive Disorder (MDD). However, the cellular and molecular substrates underlying this dysfunction remain unknown. Here, cell-population-specific chromatin accessibility profiling in human OFC unexpectedly mapped genetic risk for MDD exclusively to non-neuronal cells, and transcriptomic analyses revealed significant glial dysregulation in this region. Characterization of MDD-specific cis-regulatory elements identified ZBTB7A - a transcriptional regulator of astrocyte reactivity - as an important mediator of MDD-specific chromatin accessibility and gene expression. Genetic manipulations in mouse OFC demonstrated that astrocytic Zbtb7a is both necessary and sufficient to promote behavioral deficits, cell-type-specific transcriptional and chromatin profiles, and OFC neuronal hyperexcitability induced by chronic stress - a major risk factor for MDD. These data thus highlight a critical role for OFC astrocytes in stress vulnerability and pinpoint ZBTB7A as a key dysregulated factor in MDD that mediates maladaptive astrocytic functions driving OFC hyperexcitability.

Identifiers

PMID37205394
PMCPMC10187272
OpenAlexW4372319395

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.