Being subjected to abuse and/or neglect by the caregiver has likewise been linked with epigenetic alterations in human populations. For example, the NR3C1 1F exon promoter exhibited enhanced levels of methylation and decreased levels of expression and transcription factor binding in the hippocampus of suicide victims with a history of childhood abuse relative to suicide victims that had not experienced abuse during childhood (McGowan et al., 2009). This finding was extended to additional splice variants of the NR3C1 gene (i.e. 1B, 1C, and 1H), which were found to be downregulated in suicide-completers with an abuse history. Further, DNA methylation at these promoter regions was correlated with transcript expression (Labonte et al., 2012). In peripheral blood, levels of methylation at the NR3C1 gene were found to be positively correlated with the amount of maltreatment sustained during childhood (Perroud et al., 2011). Because of the role GRs play in terminating HPA axis activity, reduced GR numbers could intensify the effects of stress and, in turn, increase the risk for stress-induced pathology in adulthood. The ribosomal RNA gene promoter was likewise found to be hypermethylated in hippocampus, but not cerebellum, of suicide-completers with a history of childhood abuse (McGowan et al., 2008).
