Evidence map›Paper›PMID 40957904›Full record

SynthesisMolecular psychiatry2026

Multi-epigenome-wide analyses and meta-analysis of child maltreatment in judicial autopsies and intervened children and adolescents.

Shota Nishitani, Takashi X Fujisawa, Shinichiro Takiguchi, Akiko Yao, Kazuhiro Murata, Daiki Hiraoka, Yoshifumi Mizuno, Keiko Ochiai, Natasha Y S Kawata, Kai Makita and 11 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in Molecular 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. Polygenic risk meets early trauma: toward a neuropsychodevelopmental model of schizophrenia.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
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

21 authors.

Shota NishitaniResearch Center for Child Mental Development, University of Fukui, Fukui, Japan. nshota@u-fukui.ac.jp.ORCID 0000-0002-6234-295X
Takashi X FujisawaResearch Center for Child Mental Development, University of Fukui, Fukui, Japan.
Shinichiro TakiguchiResearch Center for Child Mental Development, University of Fukui, Fukui, Japan.ORCID 0000-0003-0911-0022
Akiko YaoResearch Center for Child Mental Development, University of Fukui, Fukui, Japan.
Kazuhiro MurataDepartment of Forensic Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Daiki HiraokaResearch Center for Child Mental Development, University of Fukui, Fukui, Japan.ORCID 0000-0003-2776-5129
Yoshifumi MizunoResearch Center for Child Mental Development, University of Fukui, Fukui, Japan.ORCID 0000-0003-2209-352X
Keiko OchiaiDivision of Developmental Higher Brain Functions, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, and University of Fukui, Osaka, Japan.
Natasha Y S KawataResearch Center for Child Mental Development, University of Fukui, Fukui, Japan.ORCID 0000-0001-7326-6529
Kai MakitaResearch Center for Child Mental Development, University of Fukui, Fukui, Japan.
Daisuke N SaitoResearch Center for Child Mental Development, University of Fukui, Fukui, Japan.
Sakae MizushimaResearch Center for Child Mental Development, University of Fukui, Fukui, Japan.ORCID 0000-0003-4500-1149
Shizuka SuzukiDepartment of Child and Adolescent Psychological Medicine, University of Fukui Hospital, Fukui, Japan.
Sawa KurataDivision of Developmental Higher Brain Functions, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, and University of Fukui, Osaka, Japan.
Naoki IshiuchiCenter for Cause of Death Investigation Research Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Daiki TaniyamaDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Naoki NakaoDepartment of Forensic Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID 0009-0004-1328-5081
Akira NameraDepartment of Forensic Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hidehiko OkazawaLife Science Innovation Center, School of Medical Sciences, University of Fukui, Fukui, Japan.ORCID 0000-0001-7046-3383
Masataka NagaoDepartment of Forensic Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Akemi TomodaResearch Center for Child Mental Development, University of Fukui, Fukui, Japan. atomoda@u-fukui.ac.jp.ORCID 0000-0002-6558-5017

Funding

Japan Agency for Medical Research and Development (AMED) JP20gk0110052
6 · The paper itself

Abstract

Child maltreatment (CM) is associated with adverse physical, psychological, and neurodevelopmental outcomes later in life. Epigenetic modifications, particularly DNA methylation, have been proposed as potential mechanisms underlying these long-term effects. To identify robust CM-associated methylation signatures, we conducted epigenome-wide analyses across three independent cohorts: judicial autopsy cases (CM:11, Controls:7), toddlers shortly after social intervention (CM:36, Controls:49), and adolescents who underwent brain MRI (CM:61, Controls:62). Each cohort was analyzed separately, followed by a meta-analysis to identify common methylation sites associated with CM exposure. The meta-analysis identified four significant CpG sites located within the ATE1, SERPINB9P1, CHST11, and FOXP1 genes. Among these, methylation of FOXP1 was consistently associated with structural brain alterations, including increased gray matter volume (GMV) in the orbitofrontal cortex (OFrC) and middle/posterior cingulate gyrus (MPCG), and decreased GMV in the occipital fusiform gyrus (OFuG). These brain regions are implicated in emotional regulation, memory retrieval, and social cognition, suggesting a potential neurobiological mechanism linking CM to later psychopathology. Furthermore, methylation risk scores (MRS) derived from these four CpGs successfully discriminated individuals who experienced early-life adversity in an independent validation dataset, achieving an area under the receiver operating characteristic curve (AUC) of 0.672, highlighting their potential utility as biomarkers. Gene ontology and pathway analyses revealed enrichment of cholinergic and glutamatergic synaptic transmission pathways, supporting their involvement in traumatic memory formation. Our findings provide novel insights into the epigenetic mechanisms underlying CM and identify potential biomarkers for early detection, prevention, and therapeutic intervention, ultimately contributing to breaking the intergenerational cycle of maltreatment.

Indexed as

Child AbuseEpigenomeAdolescentAutopsyBrainChildChild, PreschoolCohort StudiesCpG IslandsDNA MethylationEpigenesis, GeneticEpigenomicsFemaleGenome-Wide Association StudyGray MatterHumans

Identifiers

PMID40957904
PMCPMC12916479

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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.