Increased DNA methylation of neuropsychiatric genes occurs in borderline personality disorder

Dammann, Gerhard; Teschler, Stefanie; Haag, Tanja; Altmüller, Franziska; Tuczek, Frederik; Dammann, Reinhard

doi:10.4161/epi.6.12.18363

Cited by 120 publications

(110 citation statements)

References 72 publications

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“…Regardless, we note that a comparable finding (i.e., hypermethylation of GR and other neuroregulatory gene promoters in individuals with BPD, regardless of presence of reported childhood abuse) has been reported elsewhere. 20 It remains to discuss an effect suggesting 1H hypomethylation in participants with concurrent BN and BPD-which, we note, corroborates a similar result obtained by one of the authors on GR region 1H in the hippocampus of suicide completers with a history of childhood abuse. 18 An implication of the preceding may be that the GR regulatory region may be poised for epigenetic regulations that run in different directions across different regions of promoter.…”

Section: Discussionsupporting

confidence: 75%

“…18,19 Such processes could explain associations between adverse environmental exposures, during early development, and later problems of adjustment. Whether or not the preceding is true, evidence associates hypermethylation of various neuroregulatory genes with diverse mental-illness phenotypes, including suicidality, 18 borderline personality disorder (BPD), 20,21 and eating disorders (EDs). [22][23][24] The Present Study…”

Section: Epigenetic Processesmentioning

confidence: 99%

“…Based on findings indicating generally altered glucocorticoid functioning in BN, 8,9 and a role of a main GR gene polymorphism in bulimic and associated phenomenology, 6,7 we explored the possibility that women with BN, when compared to noneating-disordered (NED) women, might display propensities toward hypermethylation of the GR gene promoter. We also explored two alternative hypotheses: The first, based on evidence linking developmental stress to altered GR methylation in animals and humans, [15][16][17][18] was that GR gene methylation might be more characteristic of individuals with BN who reported exposure to childhood abuse than of people with BN alone; the second, based on studies associating suicidality 18 and BPD 20,21 with increased GR gene methylation, was that GR methylation might be more pronounced in individuals with BN who also displayed comorbid ''borderline'' or ''suicidal'' manifestations, than of people with BN alone. Guided by previous findings, we targeted CpG sites in GR gene first exon sites 1B, 1C, 1F, and 1H, 16,18 measuring percent methylation at each CpG.…”

Section: Epigenetic Processesmentioning

confidence: 99%

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

Steiger

Labonté

Groleau

et al. 2013

Intl J Eating Disorders

113

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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.

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Section: Discussionsupporting

confidence: 75%

Section: Epigenetic Processesmentioning

confidence: 99%

Section: Epigenetic Processesmentioning

confidence: 99%

See 1 more Smart Citation

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

Steiger

Labonté

Groleau

et al. 2013

Intl J Eating Disorders

113

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“…Despite the vulnerability of the HPA axis to early stress [17,18] and its involvement in BPD pathogenesis [19], only a few studies on the contribution of HPA axis genetic alterations have been published [20][21][22]. These studies all focus on epigenetic mechanisms, while the presence of risk sequence polymorphisms has not been investigated.…”

Section: Introductionmentioning

confidence: 96%

The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder

Martín-Blanco

Ferrer

Soler

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus-pituitary-adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case-control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder.

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“…COMT genes was found in borderline personality disorder but activity was not measured (Dammann et al, 2011).…”

Section: Human Genetic and Epigenetic Variationsmentioning

confidence: 99%

Molecular aspects of monoamine oxidase B

Ramsay

2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Graphical abstract Highlights• MAO B activity depends on both amine and oxygen concentrations KeywordsMonoamine oxidase B; kinetics; drug design; neurotransmitter levels; platelet AbbreviationsAlzheimer's Disease, AD; Parkinson's Disease, PD; dopamine transporter, DAT; serotonin transporter, SERT; noradrenaline transporter, NET; the vesicular transporter, VMAT; Gprotein coupled receptor, GPCR; induced pluripotent stem cells, iPSC; serotonin reuptake inhibitor, SSRI; brain-derived neurotrophic factor, BDNF; multi-target designed ligands, MTDL; IC 50 , the concentration of compound required to inhibit a specified assay by 50%; K i , a kinetically measured inhibitor dissociation constant. Word count -approx 5490 (excluding references). Abstract 196 words.3

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Increased DNA methylation of neuropsychiatric genes occurs in borderline personality disorder

Cited by 120 publications

References 72 publications

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

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

The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder

Molecular aspects of monoamine oxidase B

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