Epigenetics in Personality Disorders: Today's Insights

Abstract

Objective: Epigenetic mechanisms have been described in several mental disorders, such as mood disorders, anxiety disorders and schizophrenia. However, less is known about the influence of epigenetic mechanisms with regard to personality disorders (PD). Therefore, we conducted a literature review on existing original data with regards to epigenetic peculiarities in connection with personality disorders.Methods: Systematic literature review using PRISMA guidelines. Search was performed via NCBI PubMed by keywords and their combinations. Used search terms included “epigenetic,” “methylation,” “acetylation” plus designations of specified personality traits and disorders according to DSM-IV.Results: Search yielded in total 345 publications, 257 thereof with psychiatric topic, 72 on personality disorder or traits, 43 of which were in humans and epigenetic, 23 thereof were original studies. Lastly, 23 original publications fulfilled the intended search criteria and were included. Those are 13 studies on gene methylation pattern with aggressive, antisocial and impulsive traits, 9 with borderline personality disorder (BPD), and 2 with antisocial personality disorder (ASPD). The results of these studies showed significant associations of PD with methylation aberrances in system-wide genes and suggest evidence for epigenetic processes in the development of personality traits and personality disorders. Environmental factors, of which childhood trauma showed a high impact, interfered with many neurofunctional genes. Methylation alterations in ASPD and BPD repeatedly affected HTR2A, HTR3A, NR3C1, and MAOA genes.Summary: Epigenetic studies in PD seem to be a useful approach to elucidate the interaction of co-working risk factors in the pathogenesis of personality traits and disorders. However, the complexity of pathogenesis leads to divergent results and impedes an explicit interpretation. Differing methylation patterns within the selected PD could indicate subgroups which would benefit from patient-oriented therapeutic adjustments. They might play a major role in the future design and observation of early therapeutic intervention and thus could help to prevent severe dysfunctional conduct or full-blown personality disorder in risk subjects.

Genome-Wide DNA Methylation Patterns in Persistent Attention-Deficit/Hyperactivity Disorder and in Association With Impulsive and Callous Traits

“…Both traits are normally distributed in the general population (Chamorro et al, 2012;Georgiev et al, 2013), and the extreme ends of their spectra are marked as maladaptive and pathological (McLennan, 2016). Both genes (Brikell et al, 2018;Moore et al, 2019) and the environment (Gescher et al, 2018;Waller et al, 2018) play important roles in the etiology of impulsive and callous traits.…”

“…Environmental adversities may act on behavior through epigenetic mechanisms (Kubota et al, 2012). Epigenetic mechanisms control gene expression downstream of both environmental and genetic (risk) factors; for example, the methylation of DNA at CpG sites can change in response to an environmental stimulus (Kubota et al, 2012), which can then influence the expression levels of genes, and some differentially methylated genes linked to impulsive and callous behaviors and related disorders like ADHD have recently been described (Waltes et al, 2016;Hamza et al, 2017;Gescher et al, 2018). Since environmental factors can play a role in the onset of ADHD and associated symptoms (Thapar and Cooper, 2016), it is to be expected that DNA methylation differs between healthy controls and people with ADHD (symptoms), which might influence the transcription of genes regulating behavior, as summarized by Palumbo and coworkers for aggressive behavior (Palumbo et al, 2018).…”

From Child Abuse to Developing Borderline Personality Disorder Into Adulthood: Exploring the Neuromorphological and Epigenetic Pathway

“…The influence of environmental stressors leading to epigenetic modification was summarized by Gescher et al in a meta-analysis published in 2018 ( Figure 2) [37]. AVP, arginine vasopressin gene; cAMP, adenosine 3',5'-cyclic monophosphatase; BDNF, brainderived neurotrophic factor gene; GR gene, glucocorticoid receptor gene; mRNA, messenger ribonucleic acid; NR3C1, nuclear receptor subfamily 3, group C, member 1; BPD, borderline personality disorder.…”

Borderline personality disorder: an update for neurologists

“…17 Epigenetic studies examine how environmental conditions affect gene expression and are increasingly being considered a promising avenue for exploring the cause of personality disorders. 18 Several small studies suggest epigenetic modifications in people with BPD in genes related to stress and neurodevelopment, with environmental factors such as childhood trauma having a measurable impact on genes responsible for neurofunctioning. 17 18 For example, people with BPD have significantly higher DNA methylation, that is, evidence of epigenetic modification, of the brain-derived neurotrophic factor gene, which is involved in neurodevelopment.…”