Subsequent enhanced responses in circulating cortisol levels and heart rate to psychosocial stress were only observed in abused women presenting with MDD in adulthood but not in abused women without MDD, despite exaggerated ACTH responses in both groups. Taken together, these findings indicate that childhood abuse precipitates pituitary sensitization with subsequent counter-regulatory adrenocortical adaptations occurring only
in abused women without MDD, which may be regarded as a potential form of resilience (Heim et al., 2008). Exposure to further life stressors may lead to the HPA axis LBH589 profile seen in the group of abused women with comorbid MDD and thus
it seems that resilience is compromised in these women. Long-term changes in HPA axis function due to experiences encountered during childhood have been widely attributed to changes in the epigenome. Early Selumetinib mw studies of Michael Meaney’s group investigating the effects of maternal behavior on the offspring’s HPA axis function in adulthood provided the first evidence for an epigenetic link between early-life experiences and life-long changes in HPA axis function (Weaver et al., 2004). Rat pups reared by high care-giving mothers exhibited a sustained DNA de-methylation in the promoter region of the GR gene within the hippocampus shortly after birth. This DNA de-methylation was associated with enhanced acetylation of lysine 9 within histone H3 and increased Egr-1 because binding, promoting gene transcription. In contrast, rats reared from low care-giving mothers had significant re-methylation of this region after birth leading to aberrant HPA axis function and anxiety-like behavior in adulthood (Weaver et al., 2004).
In later studies it was found that maternal care also resulted in de-methylation of the region responsible for maternal behavior in female offspring, namely the estrogen receptor alpha 1b of the medial preoptic area (Champagne et al., 2006). These epigenetic changes in the estrogen receptor determined which class of care-giver female pups would become based on their experience as pups. Hence, female offspring of low care-giving dams would become low care-giving dams and propagate the cycle of epigenetic changes based on maternal care (Champagne et al., 2006). Other components of the HPA axis have been investigated for epigenetic changes as a result of early life stress (ELS) including the proopiomelanocortin (POMC) gene which is responsible for producing the pro-hormone for ACTH production (Patchev et al., 2014).