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In studies of animals (NEJM JW Psychiatry Sep 23 2004) and humans (NEJM JW Psychiatry Mar 30 2009), early-life stress or trauma affected the hypothalamic-pituitary-adrenal axis, including increased methylation, which reduces glucocorticoid receptor (GR) functioning. Whether stress during adolescence is associated with methylation has not been studied. To fill this knowledge gap, researchers genotyped GR methylation at three sites on the NR3C1 gene in 468 teenagers (mean age, 16; 50% female) who were participating in a larger longitudinal study. Participants with higher risk for psychopathology were oversampled.
Methylation of NR3C1 was significantly greater in individuals with trauma histories from birth to age 16 (e.g., sexual or severe phy…