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

Abstract

Objective: To compare levels of methylation of the glucocorticoid receptor (GR) gene (NR3C1) promoter between women with bulimia nervosa (BN) and women with no eating disorder (ED), and also to explore, in women with BN, the extent to which methylation of the GR gene promoter corresponds to childhood abuse, suicidality, or borderline personality disorder (BPD). Method:We measured methylation levels in selected NR3C1 promoter regions using DNA obtained from lymphocytes in 64 women with BN (32 selected as having a history of severe childhood abuse and 32 selected as having no such history) and 32 comparison women with no ED or history of childhood abuse.Results: Compared to noneating disordered women, women with BN and comorbid BPD (or BN with a history of suicidality) showed significantly more methylation of specific exon 1C sites. There was also a (nonsignificant) result indicative of greater methylation in some 1C sites among women with BN, when compared (as a group) to women with no ED. No parallel effects owing to childhood abuse were observed. Discussion: Our findings associate BN (when accompanied by BPD or suicidality) with hypermethylation of certain GR exon 1C promoter sites. We discuss theoretical and clinical implications of our findings. V V C 2013 by Wiley Periodicals, Inc.

Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review

“…Additionally, Yehuda et al (2014) reported mean hypomethylation of 1 F promoter in PTSD subjects. In contrast to the findings reviewed above, Steiger et al (2013) found no associations between 1 F methylation and either BPD, history of suicidality or childhood abuse.…”

“…Additionally, a second research group (De Rooij et al, 2012) analyzed a region specifically spanning exon 1 C (excluding its promoter region from the analysis). Steiger et al (2013) found no epigenetic correlates of experiencing childhood abuse in BN subjects with or without BPD. Nevertheless, they did observe a set of differential CpG-specific hypermethylation patterns in both BN-BPD subjects when compared to controls without eating disorders, and in BN individuals with a history of suicidality when compared to controls.…”

“…Two of the four studies that examined region 1 B methylation found no association with prenatal stress (Hompes et al, 2013) or either childhood abuse or clinical severity (Steiger et al, 2013). Intriguingly, both the papers that did report associations between psychopathology (either suicide completion or PTSD) and DNA methylation were authored by Labonté et al (2014Labonté et al ( , 2012 and cover a gene region placed immediately before exon 1 E , including its putative promoter and the whole exon 1 J .…”

“…Three of the four studies specifically examining promoter and region 1 C methylation were performed by the same research group (Labonté et al, 2014(Labonté et al, , 2012Steiger et al, 2013) and cover similar regions encompassing 59 CpG sites; 11 of them have been reported to be individually associated with either stress or psychiatric variables. Additionally, a second research group (De Rooij et al, 2012) analyzed a region specifically spanning exon 1 C (excluding its promoter region from the analysis).…”

Effects of cortisol on cognition in major depressive disorder, posttraumatic stress disorder and borderline personality disorder - 2014 Curt Richter Award Winner

“…One study for example reported a significant positive correlation between methylation status of the promoter region of the glucocorticoid receptor gene clinical severity (MartinBlanco et al, 2014). Another study showed that in a sample of bulimic patients comorbid BPD was associated with significantly more methylation (Steiger et al, 2013). Future research is warranted here.…”