Cited by 74Child Abuse and TraumaEpigenetics and DNA MethylationPosttraumatic Stress Disorder Research

Epigenetic alterations associated with childhood trauma and adult mental health outcomes: A systematic review

Nöthling, Jani, Malan-Müller, Stefanie, Abrahams, Naeemah, Hemmings, Sian Megan Joanna, Seedat, Soraya·2020·The World Journal of Biological Psychiatry

Abstract

Objectives: Multiple, chronic and repeated trauma exposure in childhood is associated with adverse mental health outcomes in adulthood. In this paper we synthesise the literature on epigenetic modifications in childhood trauma (CT) and the mediating effects of differential epigenetic mechanisms on the association between CT and the later onset of psychiatric disorders. Methods: We reviewed the literature up to March 2018 in four databases: PubMed, Web of Science, EBSCOhost and SCOPUS. Non-human studies were excluded. All studies investigating CT exposure both in healthy adults (18 years and older) and adults with psychiatric disorders were included. Results: Thirty-six publications were included. For mood disorders, methylation of the glucocorticoid receptor NR3C1 gene, specifically at the NGFI-A binding site in exon 1F, and correlation with CT was a robust finding. Several studies documented differential methylation of SLC6A4 , BDNF, OXTR and FKBP5 in association with CT. Common pathways identified include neuronal functioning and maintenance, immune and inflammatory processes, chromatin and histone modification, and transcription factor binding. Conclusions: A variety of epigenetic mediators that lie on a common pathway between CT and psychiatric disorders have been identified, although longitudinal studies and consistency in methodological approach are needed to disentangle cause and effect associations.

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Crossref · 10.1080/15622975.2019.1583369

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  • There are other candidate genes with at least some data in childhood trauma and epigenetic alterations, such as COMT, IL-6, and OXTR.

    “There are other candidate genes with at least some data in childhood trauma and epigenetic alterations, such as COMT, IL-6 (188), and OXTR (189).”
  • Usage of modified CRISPR-cas9 system has been expanded beyond genome editing, to RNA targeting, chromatin topology, chromatin imaging, developmental trajectories and lineage tracing.

    “In fact, usage of a modified CRISPR-cas9 system has been expanded beyond genome editing, to RNA targeting, chromatin topology, chromatin imaging, and developmental trajectories as well as to lineage tracing (188, 304).”
  • Differential DNA methylation profiles are associated with exposure to childhood adversity and cannabis use.

    “Indeed, recent parallel evidence suggests that differential DNAm profiles are associated with exposure to childhood adversity (CA) as well as cannabis use (CU) (Kandaswamy et al., 2020; Markunas et al., 2020; Nöthling, Malan-Müller, Abrahams, Hemmings, & Seedat, 2020).”

    From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Nöthling, Malan-Müller, Abrahams, Hemmings, & Seedat, 2020

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References 123 · Cited by 74

Authors
Nöthling, J., Malan-Müller, S., Abrahams, N., Hemmings, S. M. J., & Seedat, S.
Affiliations
  • South African Medical Research Council (ZA)
  • Department of Psychiatry, Stellenbosch University, Cape Town, South Africa; Gender and Health Research Unit, South African Medical Research Council, Cape Town, South Africa
Corresponding author
Nöthling, Jani
Venue
The World Journal of Biological Psychiatry
Published
2019-04-02
Volume
21
Issue
7
Pages
493-512
ISSN
  • 1562-2975 (ISSN-L)
  • 1814-1412
OpenAlex
W2916883774
Cited by
74
References
123
Citations by year
2026: 8 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 9 · 2021: 8 · 2020: 13 · 2019: 3 · 2017: 1
FWCI
1.30
Type
journal article
Language
en
Open access
closed
Locations
  • The World Journal of Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
The South African Research Chair (10)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Keywords
childhood trauma, epigenetic modifications, DNA methylation, adult mental health, mental illness, serotonin transporter, brain-derived neurotrophic factor, oxytocin receptor, FKBP5, mood disorders, transcription factor binding
MeSH terms
Adult, Mental Disorders, Child, Child Abuse, Humans, Mental Health, Receptors, Glucocorticoid, DNA Methylation, Epigenesis, Genetic, Serotonin Plasma Membrane Transport Proteins

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