Evidence map›Paper›PMID 41192574›Full record

ArticleBiological psychiatry2026

Mapping DNA Methylation Signatures to Identify Epigenetic Variation Across Subcortical Regions of the Human Posttraumatic Stress Disorder Brain.

Hongyu Li, Yujing Liu, Yiming Shi, Jiawei Wang, Tuan P Nguyen, Yuhan Xie, Wangjie Zheng, Youshu Cheng, Dianne A Cruz, Jennifer L Modliszewski and 25 more

Abstract read
In one paragraph

Article in Biological psychiatry, 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

35 authors.

Hongyu LiDepartment of Biostatistics, Yale University School of Public Health, New Haven, Connecticut.
Yujing LiuDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Yiming ShiDepartment of Biostatistics, Yale University School of Public Health, New Haven, Connecticut.
Jiawei WangDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Tuan P NguyenDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Yuhan XieDepartment of Biostatistics, Yale University School of Public Health, New Haven, Connecticut.
Wangjie ZhengDepartment of Biostatistics, Yale University School of Public Health, New Haven, Connecticut.
Youshu ChengDepartment of Biostatistics, Yale University School of Public Health, New Haven, Connecticut.
Dianne A CruzDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
Jennifer L ModliszewskiDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
Rosemarie TerwilligerDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Alexa-Nicole SlibyDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
José Jaime Martínez-MagañaDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; National Center for PTSD, United States Department of Veterans Affairs, West Haven, Connecticut.
Janitza L Montalvo-OrtizDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; National Center for PTSD, United States Department of Veterans Affairs, West Haven, Connecticut.
John D RoacheResearch and Development Service, South Texas Veterans Health Care System, San Antonio, Texas.
Lynnette A AverillDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas.
Stacey Young-McCaughanDepartment of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Research and Development Service, South Texas Veterans Health Care System, San Antonio, Texas.
Paulo R ShiromaMinneapolis VA Medical Center and the Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.
Bertrand R HuberPathology and Laboratory Medicine, Veterans Affairs Boston Healthcare System, Boston, Massachusetts.
David A LewisDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Jill GlausierDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Paul HoltzheimerNational Center for PTSD, United States Department of Veterans Affairs, West Haven, Connecticut; Department of Psychiatry, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
Matthew J FriedmanNational Center for PTSD, United States Department of Veterans Affairs, West Haven, Connecticut; Department of Psychiatry, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
Jing ZhangDepartment of Computer Science, University of California, Irvine, Irvine, California.
Alan L PetersonDepartment of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Research and Development Service, South Texas Veterans Health Care System, San Antonio, Texas.
Chadi G AbdallahDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas.
Amir ValizadehDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; National Center for PTSD, United States Department of Veterans Affairs, West Haven, Connecticut.
Xinyu ZhangDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; National Center for PTSD, United States Department of Veterans Affairs, West Haven, Connecticut.
Ke XuDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; National Center for PTSD, United States Department of Veterans Affairs, West Haven, Connecticut.
John H KrystalDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; National Center for PTSD, United States Department of Veterans Affairs, West Haven, Connecticut.
Ronald S DumanDeceased.
Hongyu ZhaoDepartment of Biostatistics, Yale University School of Public Health, New Haven, Connecticut.
David L CorcoranDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina.
Douglas E WilliamsonDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina; Durham VA Healthcare System, Durham, North Carolina. Electronic address: williamson@duke.edu.
Matthew J GirgentiDepartment of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; National Center for PTSD, United States Department of Veterans Affairs, West Haven, Connecticut. Electronic address: matthew.girgenti@yale.edu.

Funding

Deciphering the single-nucleus genomic regulatory structure of opioid use disorder in the human brainDP1DA058737 · NIDA · YALE UNIVERSITY · PI Janitza Liz Montalvo-Ortiz · 2023 to 2026
$2.0M
Molecular Dissection of Alcohol Use Disorder Through Targeted Brain Multi-omicsR01AA031017 · NIAAA · YALE UNIVERSITY · PI Matthew J Girgenti · 2024 to 2026
$1.7M
Functional convergence following disruption of diverse genes associated with cannabis use and major depressionDP1DA060811 · NIDA · YALE UNIVERSITY · PI Matthew J Girgenti · 2024 to 2026
$1.3M
Integrative Epigenomic Mapping of Co-Morbid OUD and PTSD SupplementR21DA050160 · NIDA · YALE UNIVERSITY · PI MONTALVO-ORTIZ, JANITZA LIZ · 2020 to 2021
$433k
CSRD VA IK2 CX002095NIAAA NIH HHS R01 AA031017NIDA NIH HHS DP1 DA058737NIDA NIH HHS DP1 DA060811NIDA NIH HHS R21 DA050160
6 · The paper itself

Abstract

backgroundPosttraumatic stress disorder (PTSD) is a mental disorder that may occur in the aftermath of severe psychological trauma. Epigenetic changes in the brain may play a critical role in understanding the neurobiology of PTSD by linking environmental traumatic stress exposure to lasting alterations in gene expression that shape neuronal function.

methodsWe examined 1,065,750 DNA methylation (DNAm) sites from 171 donors including neurotypical controls and PTSD and major depressive disorder (MDD) cases across 6 regions implicated in the fear circuitry of the brain. We performed RNA sequencing (RNA-seq) to examine changes in gene expression and linked these changes to changes in DNAm at nearby sites in a case-control manner. We created a single cell-type atlas of DNAm using a single-nucleus RNA-seq reference panel to map epigenetic changes to specific cell types. Finally, we leveraged a human PTSD ketamine trial to associate blood DNAm biomarkers of ketamine efficacy with specific changes in DNAm in the brain.

resultsWe found significant differential methylation for PTSD near 195 genes, and to further resolve the changes we observed, we constructed a cell type-specific DNAm atlas defined for changes to the PTSD methylome across 6 cell types. To identify potential therapeutic intersections for PTSD, we found significant methylation levels in the MAD1L1, ELFN1, and WNT5A genes in patients with PTSD who responded to ketamine. Finally, to better understand the unique biology of PTSD, we analyzed matching methylation data for a cohort of donors with MDD with no known history of trauma or PTSD.

conclusionsOur results implicate DNAm as an epigenetic mechanism underlying the molecular changes associated with the subcortical fear circuitry of the PTSD brain.

Indexed as

BrainDNA MethylationEpigenesis, GeneticMajor Depressive DisorderStress Disorders, Post-TraumaticAdultCase-Control StudiesFemaleHumansMaleMiddle AgedSequence Analysis, RNAAmygdalaDNA methylationHippocampusMajor depressive disorderPTSD

Identifiers

PMID41192574
PMCPMC12862789

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.