There are precedents for the apparent developmental origins for the observed differences in DNA methylation and glucocorticoid receptor expression. Childhood abuse in humans is associated with altered hippocampal development39, enhanced HPA activity9,11 and an increased risk for psychopathology15,16. Similarly, children exposed to childhood adversity are more likely to engage in suicidal behavior40,41. Variations in the parental care of children are linked with individual differences in HPA and sympathetic and central catecholamine responses to stress1,11,42,43. Interventions that target parental care of high-risk children alter HPA activity44. Thus, it is tempting to speculate that epigenetic processes might mediate the effects of the social environment during childhood on hippocampal gene expression and that stable epigenetic marks such as DNA methylation might then persist into adulthood and influence the vulnerability for psychopathology through effects on intermediate levels of function, such as HPA activity.
