Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse

In response to stress, the brain signals the adrenal gland to release hormones, including glucocorticoid, and hence its proper levels are important for normal function and to preserve physiological equilibrium. In rats, it has been found that there is a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression. In humans, a recent study by Patrick O McGowan, et al. suggests a link between childhood abuse and decreased hippocampal glucocorticoid receptor expression along with increased hypothalamic-pituitary-adrenal (HPA) activity. They observed that the hippocampal samples from suicide victims with a history of childhood abuse showed increased methylation of the exon 1F NR3C1 promoter, in comparison with suicides with no history of childhood abuse. They suggest that the increased methylation caused lower levels of glucocorticoid receptor to be produced which hindered the capability to handle stress. These altered HPA stress responses may have lead to an increased risk of suicide. The main interpretation for such findings is that childhood adversity might alter the development of systems that serve to regulate stress responses, such as hippocampal glucocorticoid receptor expression, and thus enhance the effect of stress in adulthood and vulnerability for mood disorders. This being proved, the challenge for the future is to understand how epigenetic variation overlaying occurring in nucleotide sequences might explain the developmental origins of vulnerability for chronic illnesses.

 

Sindhu Igoor