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.
Highlights
Abundant research has demonstrated the role of negative life events, including traumatic childhood experiences for the development of stress-related psychiatric disorders [1]
Mean methylation levels averaged for all CpGs were lower in patients with borderline-personality disorder (BPD) compared to the HC group (BPD: % methylation M = 0.66%, standard deviations (SD) = 0.17; mean-centered M = -0.08, SD = 0.22; mean rank = 37.87; HC: % methylation M = 0.74%, SD = 0.14; mean centered M = 0.08, SD = 0.29; mean rank = 52.30; U = 669.0, p = 0.008 with effect size d = 0.583)
Significant correlations are printed in bold, correlation surviving correction due to multiple correction are marked with
Summary
Abundant research has demonstrated the role of negative life events, including traumatic childhood experiences for the development of stress-related psychiatric disorders [1]. Childhood maltreatment is known to affect the hypothalamic-pituitary-adrenal (HPA) stress response, with newer research suggesting that epigenetic alteration (e.g., methylation or histone acetylation) of genes involved in the regulation of steroid turnover is critically involved [2,3]. The NR3C1 gene encodes for the glucocorticoid receptor (GR), which is the main binding site of cortisol. FKBP 52 is a co-chaperone for Hsp 90 which reduces translocation of the GR-complex [8,9,10]. Activation of the GR leads to fast FKBP5 induction and binding to the GR-complex, which results in a decrease in cortisol affinity of the GR and reduced translocation to the nucleus. FKBP5 modulates the sensitivity of the GR and is suggested to act as a short negative feedback loop [4,5,11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
