Changes in genes and fearful behavior caused by early life stress can be reversed.

The information in our genes can be permanently altered by 'epigenetic' modifications, such as adding methyl groups to DNA. Infant rats that receive abundant licking and grooming from their mothers in their first week of life show increased methylation of their glucocorticoid receptor (GR) genes, and increased production of the GR in several tissues involved in the hypothalamic-pituitary-adrenal (HPA) response to stress. Infants that do not receive as much care show decreased methylation and are more fearful as adults under conditions of stress. Weaver et al. centrally infused the brains of these more fearful adults with the essential amino acid L-methionine, a precursor to S-adenosyl-methionine that serves as the donor of methyl groups for DNA methylation. They found that methionine infusion reversed the effect of maternal behavior on DNA methylation, GR expression, and hypothalamic-pituitary-adrenal and behavioral responses to stress, suggesting a causal relationship among epigenomic state, GR expression, and stress responses in the adult offspring. Their results demonstrate that, despite the inherent stability of the epigenomic marks established early in life through behavioral programming, they are potentially reversible in the adult brain.