Association between childhood maltreatment, psychopathology and DNA methylation of genes involved in stress regulation: Evidence from a study in Borderline Personality Disorder

Abstract

Previous research suggests that childhood maltreatment is associated with epigenetic modification of genes involved in hypothalamic-pituitary-adrenal (HPA) functioning, which could cause dysregulation of the stress response system. If pervasive, this may be associated with the development of stress-related disorder in adults, including affective disorders, anxiety disorders, post-traumatic stress disorder (PTSD) or borderline-personality disorder (BPD). The majority of studies have focused on DNA methylation of the glucocorticoid receptor gene (NR3C1) and the FKBP5 encoding gene, which regulates the sensitivity of the glucocorticoid receptor (GR). How methylation of NR3C1 and FKBP5 interferes with childhood adversity and psychopathology as well as empathy is an under-researched issue. Here, we sought to investigate the association of childhood maltreatment in a sample of 89 individuals (44 healthy participants and 45 patients diagnosed with BPD) with the methylation of the 1F promoter region of NR3C1 and the intron 7 of FKBP5 as well as with different measures of psychopathology and empathy. Methylation of FKBP5 (bin 2) correlated with anxiety (SCL-90-R) and the global psychopathological symptom load index (GSI), as well as with lower empathic perspective-taking abilities. Psychopathology and empathy impairments correlated with the level of childhood maltreatment. No difference in FKBP5 methylation was observed between the clinical and the non-clinical group. Methylation of NR3C1 was lower in BPD patients compared to controls, yet with small differences. The results are discussed regarding their biological relevance, including possible evolutionary explanations. In short, the regulation of the GR sensitivity by methylation of FKBP5 correlated with psychopathology and empathy scores, while no correlation emerged with the severity of childhood adversity.

Potential epigenetic mechanisms in psychotherapy: a pilot study on DNA methylation and mentalization change in borderline personality disorder

“…Furthermore, lower empathic perspective-taking abilities and anxiety correlated with childhood maltreatment. Although this study does not find differences between clinical and non-clinical samples, it reveals the relationship between empathy engagement and FKBP5 DNA methylation (Flasbeck and Brüne, 2021).…”

Associations between childhood maltreatment and DNA methylation of the oxytocin receptor gene in immune cells of mother–newborn dyads

“…Based on intergenerational observations, the long-neglected evolutionary theory of Lamarckian inheritance is currently being re-discussed. Epigenetic modifications, and the consequent regulation of the gene expression, offer a plausible mechanism for acquired biological traits and behavioral adaptations to endure throughout generations [ 30 ]. Here, the oxytocinergic system has been proposed as a possible mediator of these CM-related intergenerational transmission effects, mainly because it is a key modulator of parenting behavior, attachment, and risk of post-partum depression [ 31 – 33 ].…”

Methylation of the Glucocorticoid Receptor Gene (NR3C1) in Adolescents with a History of Childhood Adversity Engaging in Non-Suicidal Self-Injury

“…In individuals suffering from post-traumatic stress disorder, a decreased methylation has been reported compared to that of a HC group [43]. A recent study focusing on methylation levels of NR3C1-1F in patients with BPD showed lower overall methylation compared to a HC group with a negative correlation between the level of methylation and ACE [44]. Overall, the majority of those studies report small to medium effect sizes.…”