Childhood maltreatment and methylation of the glucocorticoid receptor gene NR3C1 in bipolar disorder
Open accessAbstract
Background: Early-life adversities represent risk factors for the development of bipolar affective disorder and are associated with higher severity of the disorder. This may be the consequence of a sustained alteration of the hypothalamic–pituitary–adrenal (HPA) axis resulting from epigenetic modifications of the gene coding for the glucocorticoid receptor ( NR3C1 ). Aims: To investigate whether severity of childhood maltreatment is associated with increased methylation of the exon? 1 F NR3C1 promoter in bipolar disorder. Method: A sample of people with bipolar disorder ( n = 99) were assessed for childhood traumatic experiences. The percentage of NR3C1 methylation was measured for each participant. Results: The higher the number of trauma events, the higher was the percentage of NR3C1 methylation (β = 0.52, 95% CI 0.46–0.59, P <<0.0001). The severity of each type of maltreatment (sexual, physical and emotional) was also associated with NR3C1 methylation status. Conclusions: Early-life adversities have a sustained effect on the HPA axis through epigenetic processes and this effect may be measured in peripheral blood. This enduring biological impact of early trauma may alter the development of the brain and lead to adult psychopathological disorder.
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The degree of GR-gene methylation was associated with childhood maltreatment.
“In another study, the degree of GR-gene methylation was associated with childhood maltreatment (Perroud et al. 2014).”
From The HPA axis in bipolar disorder: Systematic review and meta-analysis (2016) · cites this paper as Perroud et al. 2014
Childhood traumatic experiences can determine epigenetic modifications of the glucocorticoid receptor gene in patients with bipolar disorder.
“childhood traumatic experiences can determine epigenetic modifications of the GR gene in patients with BD (Perroud et al. 2014;Fish et al. 2004).”
From The HPA axis in bipolar disorder: Systematic review and meta-analysis (2016) · cites this paper as Perroud et al. 2014
Childhood maltreatment associates with an increased level of exon 1F methylation in peripheral blood lymphocytes.
“Perroud et al127,128 used peripheral blood lymphocytes to show that childhood maltreatment associates with an increased level of exon 1F methylation”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [127]
The results are consistent with previous research in adult humans demonstrating an association between child abuse and methylation differences.
“our results are consistent with previous research in adult humans demonstrating an association between child abuse and methylation differences, despite differences in sample characteristics”
From Associations Between Early Life Stress and Gene Methylation in Children (2015) · cites this paper as Perroud et al., 2014
The current data replicate previously demonstrated associations between child maltreatment and methylation of the GR gene.
“The fact that the current data replicate previously demonstrated associations between child maltreatment and methylation of the GR gene”
From Associations Between Early Life Stress and Gene Methylation in Children (2015) · cites this paper as Perroud et al., 2014
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- Authors
- Perroud, N., Dayer, A., Piguet, C., Nallet, A., Favre, S., Malafosse, A., & Aubry, J.-M.
- Affiliations
- University of Geneva (CH)
- University Hospital of Geneva (CH)
- Corresponding author
- Perroud, Nader
- Venue
- British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 2014-01
- Volume
- 204
- Issue
- 1
- Pages
- 30-35
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- OpenAlex
- W2123497401
- Cited by
- 89
- References
- 32
- Citations by year
- 2024: 4 · 2023: 1 · 2022: 1 · 2021: 8 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 12 · 2016: 12 · 2015: 16 · 2014: 21 · 2013: 4
- FWCI
- 19.63
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- retraction (2014-08-01)
- Open access
- bronze
- doi.org
- Locations
- The British Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (132853)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- child abuse, NR3C1, glucocorticoid receptor, DNA methylation, bipolar disorder, childhood adversity, hypothalamic-pituitary-adrenal axis, epigenetics, injury severity, physical abuse, emotional abuse, sexual abuse, peripheral blood biomarkers
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