Borderline personality disorder and childhood maltreatment: A genome-wide methylation analysis
Open accessAbstract
Early life adversity plays a critical role in the emergence of borderline personality disorder (BPD) and this could occur through epigenetic programming. In this perspective, we aimed to determine whether childhood maltreatment could durably modify epigenetic processes by the means of a whole-genome methylation scan of BPD subjects. Using the Illumina Infinium® HumanMethylation450 BeadChip, global methylation status of DNA extracted from peripheral blood leucocytes was correlated to the severity of childhood maltreatment in 96 BPD subjects suffering from a high level of child adversity and 93 subjects suffering from major depressive disorder (MDD) and reporting a low rate of child maltreatment. Several CpGs within or near the following genes (IL17RA, miR124-3, KCNQ2, EFNB1, OCA2, MFAP2, RPH3AL, WDR60, CST9L, EP400, A2ML1, NT5DC2, FAM163A and SPSB2) were found to be differently methylated, either in BPD compared with MDD or in relation to the severity of childhood maltreatment. A highly relevant biological result was observed for cg04927004 close to miR124-3 that was significantly associated with BPD and severity of childhood maltreatment. miR124-3 codes for a microRNA (miRNA) targeting several genes previously found to be associated with BPD such as NR3C1. Our results highlight the potentially important role played by miRNAs in the etiology of neuropsychiatric disorders such as BPD and the usefulness of using methylome-wide association studies to uncover such candidate genes. Moreover, they offer new understanding of the impact of maltreatments on biological processes leading to diseases and may ultimately result in the identification of relevant biomarkers.
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This result was validated via pyrosequencing and hypothesized to reflect the critical role of neuronal development and HPA axis regulation under epigenetic control, given that miR-124-3 targets NR3C1 and the mineralocorticoid receptor (NR3C2).
“This result was validated via pyrosequencing and hypothesized to reflect the critical role of neuronal development and HPA axis regulation under epigenetic control, given that miR 124-3 targets NR3C1 and the mineralocorticoid receptor (NR3C2) (Prados et al., 2015).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Prados et al., 2015
An EWAS comparing all-female BPD patients (n=96) with a history of high childhood adversity to MDD patients (n=93) reporting low rates of childhood maltreatment highlighted a CpG site close to miR-124-3, where hypomethylation was linked to BPD and increased childhood trauma.
“A surprising result arose from an EWAS investigation comparing an all-female set of patients with BPD (n=96) and a history of high childhood adversity to patients with MDD (n=93) reporting low rates of childhood maltreatment: comparison of BPD to MDD and low to high childhood trauma severity in multi-and univariate analyses highlighted a CpG site close to miR 124-3, where hypomethylation was”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Prados et al., 2015
Methylation at miR124-3 CpG site is decreased in association with increased childhood maltreatment.
“↓ Methylation at miR124-3 CpG site associated with increased childhood maltreatment”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Prados et al., 2015
A number of EWAS studies conducted in clinical samples have reported an association between exposure to childhood adversity and DNAm changes across genes involved in inflammation.
“A number of EWAS studies conducted in clinical samples have reported an association between exposure to CA and DNAm changes across genes involved in inflammation.”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Prados et al., 2015
A study found a positive correlation between the IL17RA DNAm and childhood adversity in a Borderline PD and MDD sample.
“For instance, a study (Prados et al., 2015) found a positive correlation between the IL17RA DNAm and CA in a Borderline PD and MDD sample.”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Prados et al., 2015
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- Authors
- Prados, J., Stenz, L., Courtet, P., Prada, P., Nicastro, R., Adouan, W., Guillaume, S., Olié, E., Aubry, J. ‐., Dayer, A., & Perroud, N.
- Affiliations
- University of Geneva (CH)
- Inserm (FR)
- University Hospital of Geneva (CH)
- Department of Emergency Psychiatry Centre Hospitalier Régional Universitaire de Montpelier, and INSERM U1061, University of Montpellier 1 France
- Corresponding author
- Perroud, N.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2015-02
- Volume
- 14
- Issue
- 2
- Pages
- 177-188
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- OpenAlex
- W2140400360
- Cited by
- 112
- References
- 51
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 6 · 2023: 10 · 2022: 6 · 2021: 13 · 2020: 15 · 2019: 8 · 2018: 14 · 2017: 8 · 2016: 14 · 2015: 5
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- Locations
- Genes Brain & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- HAL (submittedVersion)
- Funders
- AXA Research Fund (None)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Personality Disorders and Psychopathology
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- borderline personality disorder, child abuse, DNA methylation, epigenetics, childhood adversity, microRNA, methylome-wide association study, major depressive disorder, biomarkers, NR3C1, peripheral blood leukocytes
- MeSH terms
- Adult, Borderline Personality Disorder, Child, Child Abuse, Major Depressive Disorder, Female, Genetic Markers, Humans, Male, Psychiatric Status Rating Scales, DNA Methylation, Genome-Wide Association Study
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