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Childhood maltreatment and methylation of the glucocorticoid receptor gene NR3C1 in bipolar disorder

  • Nader Perroud (a1), Alexandre Dayer (a2), Camille Piguet (a3), Audrey Nallet (a4), Sophie Favre (a4), Alain Malafosse (a5) and Jean-Michel Aubry (a6)...
  • Please note a retraction has been issued for this article.
Abstract
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? 1F 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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Copyright
Corresponding author
Nader Perroud, TRE Programme, Service of Psychiatric Specialties, University Hospitals of Geneva (HUG), 22 rue de Lausanne, 1202 Geneva, Switzerland. Email: nader.perroud@hcuge.ch
Footnotes
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Joint first authors.

∗∗

joint last authors.

See editorial, pp. 3–5, this issue.

This research was supported by grants from the Swiss National Foundation (32003B_125469/1 and by the NCCR Synapsy to J.M.A.; 320030_132853 to A.M.) and by the AXA Research Foundation to A.M. C.P. is supported by a grant from the Swiss National Science Foundation.

Declaration of interest

None.

Footnotes
References
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Childhood maltreatment and methylation of the glucocorticoid receptor gene NR3C1 in bipolar disorder

  • Nader Perroud (a1), Alexandre Dayer (a2), Camille Piguet (a3), Audrey Nallet (a4), Sophie Favre (a4), Alain Malafosse (a5) and Jean-Michel Aubry (a6)...
  • Please note a retraction has been issued for this article.
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