Our findings are also consistent with those from studies with rodent and nonhuman primates showing that persistent disruptions of mother-infant interactions are associated with increased hypothalamic corticotrophin-releasing hormone expression and increased HPA responses to stress1,2,29. Variations in maternal care in the rat influence hippocampal glucocorticoid receptor expression, as well as methylation of the rat fetal calf serum Nr3c1 promoter, the homolog of the human exon 1F NR3C1 promoter3,4,17,22. Hippocampal samples from suicide victims showed increased methylation of the exon 1F NR3C1 promoter in comparison with samples from controls, but only in cases with a history of childhood abuse. Neither hippocampal glucocorticoid receptor expression nor the methylation status of the exon 1F NR3C1 promoter was altered in suicide victims with no history of abuse. These findings suggest that variation in the methylation status of the exon 1F NR3C1 promoter, similar to that for glucocorticoid receptor 1F and total glucocorticoid receptor mRNA expression, associates with childhood adversity and not with suicide per se.
