Evidence map›Paper›PMID 42567159›Full record

ArticleNeuron2026

Early-life stress alters H3K4me1 in VTA to prime stress sensitivity.

Hye Ji J Kim, Luke T Geiger, Julie-Anne Balouek, Lisa Z Fang, Mason R Barrett, Jeremy M Thompson, Lorna A Farrelly, Travis Hage, Rixing Lin, Andy S Chen and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2026. 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. Early life stress primes future stress vulnerability.Nature reviews. Neuroscience · 2026
    Article
  2. Altered Postnatal Chromatin Development in the Nucleus Accumbens Primes Enduring Stress Sensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Hye Ji J KimPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA.
Luke T GeigerPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA.
Julie-Anne BalouekPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA.
Lisa Z FangDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
Mason R BarrettDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO 63110, USA; Departments of Psychiatry and Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63110, USA.
Jeremy M ThompsonDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
Lorna A FarrellyNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Travis HageDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
Rixing LinPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA.
Andy S ChenPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA.
Megan TangPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA.
Hao HuangPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA.
Anna BurettaPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA.
Agatha ChanPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA.
Shannon N BennettPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA.
Benjamin A GarciaDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ian MazeNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Howard Hughes Medical Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Meaghan C CreedDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO 63110, USA; Departments of Psychiatry and Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63110, USA. Electronic address: meaghan.creed@wustl.edu.
Catherine Jensen PeñaPrinceton Neuroscience Institute, Princeton University, Princeton University, Princeton, NJ 08544, USA. Electronic address: cpena@princeton.edu.

Funding

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
Epigenetic priming of response to future stressorsR01MH129643 · NIMH · PRINCETON UNIVERSITY · PI Catherine Jensen Pena · 2022 to 2026
$3.8M
Ventral pallidal transcriptional adaptations underlying punishment-resistant opioid intakeR01DA056829 · NIDA · WASHINGTON UNIVERSITY · PI Meaghan C Creed, Vijay K Samineni · 2023 to 2026
$3.2M
Quantitative mass spectrometry for comprehending epigenetic mechanisms in a new underlying neurological developmental disorderR01HD106051 · NICHD · WASHINGTON UNIVERSITY · PI Benjamin A Garcia · 2022 to 2026
$2.6M
Dissecting ventral pallidal plasticity in punishment-resistant opioid self-administrationR01DA058755 · NIDA · WASHINGTON UNIVERSITY · PI Meaghan C Creed · 2023 to 2026
$2.5M
Dissecting the role of ventral pallidal projections to nucleus accumbens in reward processingR01DA049924 · NIDA · WASHINGTON UNIVERSITY · PI CREED, MEAGHAN C · 2020 to 2024
$2.0M
Epigenetic and cellular markers of stress sensitization by early life stress in miceR00MH115096 · NIMH · PRINCETON UNIVERSITY · PI PENA, CATHERINE JENSEN · 2019 to 2021
$746k
Epigenetic and cellular markers of stress sensitization by early life stress in miceK99MH115096 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI PENA, CATHERINE JENSEN · 2017 to 2018
$178k
NICHD NIH HHS R01 HD106051NIDA NIH HHS R01 DA049924NIDA NIH HHS R01 DA056829NIDA NIH HHS R01 DA058755NIMH NIH HHS K99 MH115096NIMH NIH HHS R00 MH115096NIMH NIH HHS R01 MH116900NIMH NIH HHS R01 MH129643
6 · The paper itself

Abstract

Early-life stress increases gene expression, neurophysiological, and behavioral responses to subsequent stress. Here, we determined the role of chromatin in such long-lasting sensitivity. We used a combination of bottom-up mass spectrometry, viral-mediated epigenome editing, RNA sequencing, patch-clamp electrophysiology of dopamine neurons, and behavioral quantification in a mouse model of early-life stress, focusing on the ventral tegmental area (VTA), a key dopaminergic brain region. We found that early-life stress enriches histone-3 lysine-4 monomethylation-associated with open chromatin and primed or active enhancers-and the H3K4 monomethylase SETD7. Mimicking early-life stress through postnatal overexpression of Setd7 and enrichment of H3K4me1 in the VTA sensitizes transcriptional, physiological, and behavioral responses to adult stress, while Setd7 knockdown ameliorates the impact of early-life stress. These findings link early-life stress experience to long-term stress hypersensitivity within the brain's dopaminergic circuitry, providing a mechanism by which early-life stress increases risk for mood and anxiety disorders later in life.

Indexed as

chromatinearly-life stressepigenetic primingepigeneticsH3K4me1histone post-translational modificationshistonesSetd7stressventral tegmental area

Identifiers

PMID42567159
PMCPMC13460783

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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.