Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma

  title={Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma},
  author={Nader Perroud and Ariane Paoloni-Giacobino and Paco Prada and Emilie Olié and Annick Salzmann and Rosetta Nicastro and S{\'e}bastien Guillaume and Dominique Mouthon and Christelle Stouder and Karen Dieben and Philippe Huguelet and Philippe Courtet and Alain Malafosse},
  journal={Translational Psychiatry},
Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid… 

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

  • N. PerroudA. Dayer J. Aubry
  • Psychology, Medicine
    The British journal of psychiatry : the journal of mental science
  • 2014
Early-life adversities have a sustained effect on the HPA axis through epigenetic processes and this effect may be measured in peripheral blood.

Methylation of the leukocyte glucocorticoid receptor gene promoter in adults: associations with early adversity and depressive, anxiety and substance-use disorders

Evidence of reduced methylation of NR3C1 in association with childhood maltreatment and depressive, anxiety and substance-use disorders in adults is presented, consistent with emerging findings, suggesting complexity in the regulation of this gene.

Methylation of the glucocorticoid receptor gene promoter in bulimic women: associations with borderline personality disorder, suicidality, and exposure to childhood abuse.

Compared to noneating disordered women, women with BN and comorbid BPD showed significantly more methylation of specific exon 1C sites, and these findings associate BN (when accompanied by BPD or suicidality) with hypermethylation of certain GR ex on 1C promoter sites.

Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment

Results indicate that maltreated children evidence higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels ofmethylation, relative to nonmaltreated preschoolers.

Glucocorticoid receptor gene (NR3C1) promoter is hypermethylated in Thai females with major depressive disorder.

Higher levels of methylation at the NR3C1 promoter may be associated with MDD in a gender-specific manner, and Bisulfite pyrosequencing on 7 CpG dinucleotides in the region showed significantly higher methylation levels in MDD patients.

Epigenetic modifications of the glucocorticoid receptor gene are associated with the vulnerability to psychopathology in childhood maltreatment

The interaction between childhood maltreatment and hGR methylation is found to be strongly correlated with an increased vulnerability to psychopathology providing evidence of epigenome × environment interactions.



Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses

Prenatal exposure to increased third trimester maternal depressed/anxious mood was associated with increased methylation of NR3C1 at a predicted NGFI-A binding site, which may offer a potential epigenetic process that links antenatal maternal mood and altered HPA stress reactivity during infancy.

Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse

Findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.

Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor

It is shown for the first time that methylation status of the GR gene of adolescent children is influenced by their mother's experience of IPV during pregnancy, which is a plausible mechanism by which prenatal stress may program adult psychosocial function.

Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood.

The findings suggest that hypothalamic-pituitary-adrenal axis and autonomic nervous system hyperreactivity, presumably due to CRF hypersecretion, is a persistent consequence of childhood abuse that may contribute to the diathesis for adulthood psychopathological conditions.

Childhood Parental Loss and Adult Hypothalamic-Pituitary-Adrenal Function

Early life influences on life-long patterns of behavior and health.

  • B. McEwen
  • Psychology
    Mental retardation and developmental disabilities research reviews
  • 2003
The findings from animal models provide a basis for understanding potential mechanisms of environmental and developmental determinants of individual differences in human stress reactivity, as well as anxiety, depression, and a host of related systemic disorders.

Preliminary Evidence for Abnormal Cortical Development in Physically and Sexually Abused Children Using EEG Coherence and MRI a

It is hypothesized that early childhood abuse or trauma could affect the development of the cerebral cortex and limbic during childhood and result in neurobiological abnormalities responsible for subsequent psychiatric disorders.

Neurobiological Consequences of Early Stress and Childhood Maltreatment: Are Results from Human and Animal Studies Comparable?

Preclinical studies on the effects of exposure to early life stress can demonstrate causality, and can enrich the understanding of the clinical research if they hypothesize that the consequences of early abuse are predominantly mediated through the induction of stress responses.

Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats

These epigenetic and transcriptional profiles constitute the first tiling microarray data set exploring the relationship between epigenetic modifications and RNA expression in both protein coding and non-coding regions across a chromosomal locus in the mammalian brain.