Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide. We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls. We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A–inducible gene transcription. These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.
Tuesday, March 03, 2009
How early abuse in humans changes the adult brain.
Studies on rat models have shown that affectionate mothering alters gene expression to dampen physiological responses to stress, while early abuse has the opposite effect. Now these basic results have been extended to humans by McGowan et al., who carried out a study of people who have committed suicide. They found that that people who were abused or neglected as children showed genetic alterations that likely made them more biologically sensitive to stress. An epigenetic regulation of the glucocorticoid receptor gene, NR3C1, is observed in humans who had been abused as children that is consistent with predictions derived from a rodent model in which early postnatal experience influences adult responses to stress. (Decreases in the expression of this receptor increase reactivity to stress.) I pass on their abstract, and here is a nice explanation of what epigenetic changes are (see also the review by Benedict Carey).