ArticleNeuron2025
Major-depressive-disorder-associated dysregulation of ZBTB7A in orbitofrontal cortex promotes astrocyte-mediated stress susceptibility.
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Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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10citing papers in PubMed, 1 pooled it
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- GATA3 drives chronic stress-induced depressive-like behaviors by reducing hippocampal CA3 pyramidal neuronal activity in male mice.Acta pharmacologica Sinica · 2026Article
- Early life experiences, the neural epigenome and affective disorder risk.Nature reviews. Neuroscience · 2026Review
- SCTR-Expressing Astrocyte-Serotonergic Neuron Signaling Drives Sexual Dimorphism in Depression Through KAT7/H4ac-Foxc2 Epigenetic Axis in an AMPK-Dependent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ZBTB18 Dysfunction Promotes Neuropathic Pain via CHD4-based Epigenetic Disinhibition of CLIC1 Channels in Sensory Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Astrocytic apelin mediates cortical neuronal function and prevents anxiety-like behaviors in mice.Acta pharmacologica Sinica · 2026Article
- Epigenetic mechanisms in traumatic brain injury: a focus on astrocytes and therapeutic implications.Journal of neuroinflammation · 2026Review
- FGF13 alleviates astrocytic apoptosis via JIP2 inhibition in the hippocampus and mitigates depression-like behavior.Journal of neuroinflammation · 2026Article
- Tracing fucosylation and astrocyte-associated pathogenic pattern in major depressive disorder: evidence from machine learning-based multi-omics and clinical validation.Frontiers in neuroscience · 2026Article
- Chronic Stress and Astrocyte Dysfunction in Depression: Molecular Mechanisms and Gene Expression Changes.Antioxidants (Basel, Switzerland) · 2025Review
Corrections and comments
- Update of
Authors and funding
29 authors.
Sasha L FultonFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Zuckerman Institute of Mind, Brain, and Behavior, Columbia University, New York, NY, USA.
Jaroslav BendlFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Giuseppina Di SalvoFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
John F FullardFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Amni Al-KachakFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ashley E LepackFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Andrew F StewartFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sumnima SinghDepartment of Cardiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Wolfram C PollerDepartment of Cardiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ryan M BastleFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Mads E HaubergCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Amanda K FakiraFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Vishwendra PatelNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Min ChenFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Romain Durand-de CuttoliFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Isabel Gameiro-RosFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Flurin CathomasFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Aarthi RamakrishnanFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 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, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Carol A TammingaDepartment of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA.
Ana MilosevicLaboratory of Developmental Genetics, Rockefeller University, New York, NY, USA.
Scott J RussoFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Filip K SwirskiDepartment of Cardiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Paul A SlesingerFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ishmail Abdus-SaboorZuckerman Institute of Mind, Brain, and Behavior, Columbia University, New York, NY, USA.
Robert D BlitzerDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Panos RoussosFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Precision Medicine and Translational Therapeutics, James J. Peters VA Medical Center, Bronx, New York, NY, USA; Mental Illness Research Education and Clinical Center, James J. Peters VA Medical Center, Bronx, New York, NY, USA.
Ian MazeFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Howard Hughes Medical Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: ian.maze@mssm.edu.
Funding
REPRESSIVE HISTONE AND DNA METHYLATION IN RODENT DEPRESSION MODELSP50MH096890 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI NESTLER, ERIC J. · 2012 to 2021
$20.2MThe 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
$5.9MMolecular 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
$4.7MRisk 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
$4.6MDefining the Differential Role of Mrgprb4+ Social Touch Somatosensory Neurons in Pain Modulation and Frontolimbic Dysregulation During Chronic Inflammatory PainK00NS125774 · NINDS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI FULTON, SASHA · 2023 to 2024
$171kInvestigating chromatin-based mechanisms of astrocyte pathology during inflammation response and stress-induced behaviorsF31MH124425 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FULTON, SASHA · 2020 to 2021
$55kCharacterizing 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
$45kHoward Hughes Medical InstituteNIMH NIH HHS F31 MH124425NIMH NIH HHS P50 MH096890NIMH NIH HHS R01 MH109677NIMH NIH HHS R01 MH116900NIMH NIH HHS U01 MH116442NINDS NIH HHS F99 NS125774NINDS NIH HHS K00 NS125774
Abstract
Heightened activity in the orbitofrontal cortex (OFC), a brain region that contributes to motivation, emotion, and reward-related decision-making, is a key clinical feature of major depressive disorder (MDD). However, the cellular and molecular substrates underlying this dysfunction remain unclear. Here, we performed cell-type-specific profiling of human OFC and unexpectedly mapped MDD-linked epigenomic features (including genetic risk variants) to non-neuronal cells, revealing significant glial dysregulation in this region. Characterization of MDD-specific chromatin loci further identified ZBTB7A-a transcriptional regulator of astrocyte reactivity-as an important mediator of MDD-related alterations. In rodent models, we found that Zbtb7a induction in astrocytes is both necessary and sufficient to drive stress-mediated behavioral deficits, cell-type-specific transcriptional/epigenomic signatures, and aberrant OFC astrocyte-neuronal communication in male mice-an established MDD risk factor. These findings thus highlight essential roles for astrocytes in OFC-mediated stress susceptibility and identify ZBTB7A as a critical and therapeutically relevant regulator of MDD-related OFC dysfunction.
Indexed as
AstrocytesDNA-Binding ProteinsMajor Depressive DisorderPrefrontal CortexStress, PsychologicalTranscription FactorsAnimalsFemaleHumansMaleMiceMice, Inbred C57BLDNA-Binding ProteinsTranscription FactorsZBTB7A protein, humananhedoniaastrocyte-neuron communicationastrocyteschronic social defeat stressepigenomicsmajor depressive disorderorbitofrontal cortexZBTB7A
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