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 (NR3C1-1_F) 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, NR3C1-1_F 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 NR3C1-1_F 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 NR3C1-1_F methylation, HPA axis deregulation, and psychopathology in a situation of child maltreatment. These results suggest that NR3C1-1_F 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: NR3C1-1_F methylation could be one mechanism that links altered HPA axis activity with the development of psychopathology.

Keywords: Child maltreatment; DNA methylation; HPA axis; NR3C1 exon 1(F); Psychopathology.