Studies in rats have established that poor maternal contact in early life, comparable to emotional neglect of children, results in HPA axis dysregulation and reduced expression of hippocampal GR gene NR3C1 resulting from hypermethylation of the promoter region (Weaver et al., 2004). Likewise, a study of postmortem hippocampus showed that suicide victims exposed to childhood maltreatment had increased methylation of an NR3C1 promoter and decreased NR3C1 expression (McGowan et al., 2009). Similarly, it is conceivable (but speculative) that our CRHBP G × E findings might be explained by the effects of childhood trauma on epigenetic modifications that influence the expression of the alternative exons and 3′UTR that is the location of the SNP cluster identified in our study (Tilgner et al., 2009).
