Child maltreatment and NR3C1 exon 1F methylation, link with deregulated hypothalamus-pituitary-adrenal axis and psychopathology: A systematic review

Abstract

Background Epigenetics offers one promising method for assessing the psychobiological response to stressful experiences during childhood. In particular, deoxyribonucleic acid (DNA) methylation has been associated with an altered hypothalamus–pituitary–adrenal (HPA) axis and the onset of mental disorders. Equally, there are promising leads regarding the association between the methylation of the glucocorticoid receptor gene (NR3C1-1F) and child maltreatment and its link with HPA axis and psychopathology. Objective The current study aimed to assess the evidence of a link among child maltreatment, NR3C1-1F methylation, HPA axis deregulation, and symptoms of psychopathology. Methods We followed the Prisma guidelines and identified 11 articles that met our inclusion criteria. Results We found that eight studies (72.72%) reported increased NR3C1-1F methylation associated with child maltreatment, specifically physical abuse, emotional abuse, sexual abuse, neglect, and exposure to intimate partner violence, while three studies (27.27%) found no significant association. Furthermore, a minority of studies (36.36%) provided additional measures of symptoms of psychopathology or cortisol in order to examine the link among NR3C1-1F methylation, HPA axis deregulation, and psychopathology in a situation of child maltreatment. These results suggest that NR3C1-1F hypermethylation is positively associated with higher HPA axis activity, i.e. increased production of cortisol, as well as symptoms of psychopathology, including emotional lability-negativity, externalizing behavior symptoms, and depressive symptoms. Conclusion NR3C1-1F methylation could be one mechanism that links altered HPA axis activity with the development of psychopathology