Abstract
Early life stress can result in persistent alterations of an individual’s stress regulation through epigenetic modifications. Epigenetic alteration of the NR3C1 gene is associated with changes in the stress response system during infancy as measured by cortisol reactivity. Although autonomic nervous system (ANS) reactivity is a key component of the stress response, we have a limited understanding of the effects of NR3C1 DNA methylation on ANS reactivity. To examine this relation, ANS stress responses of term, 4–5-month-old healthy infants were elicited using the face-to-face still-face paradigm, which involved five, 2-min episodes. Two of these episodes were the “still-face” in which the mother was non-responsive to her infant. EKG was acquired continuously and analyzed in 30 s-intervals. Cheek swabs were collected, and DNA was extracted from buccal cells. Respiratory sinus arrhythmia (RSA) was measured as heart rate variability (HRV). Mean HRV was calculated for each 30-s “face to face” episode. DNA methylation of NR3C1 was calculated using bisulfite pyrosequencing. Percent DNA methylation was computed for each of the 13 NR3C1 CpG sites. The relations between mean HRV for each “face to face” episode and percent DNA methylation was examined averaged over CpG sites 1–6 and 7–13 and at each individual CpG site. Higher HRV at baseline, first reunion, and second still-face was related to greater methylation of NR3C1 CpG sites 1–6. Higher HRV at the second reunion was related to greater methylation of NR3C1 CpG sites 12 and 13. These data provide evidence that increased methylation of NR3C1 at CpG sites 12 and 13 are associated with increased activation of parasympathetic pathways as represented by increased HRV.
Highlights
Adversity can result in persistent alterations of an individual’s physiological stress response due, in part, to epigenetic changes
We studied Respiratory sinus arrhythmia (RSA) in 4–5-month-old infants during a face-toface still-face paradigm that included an episode in which the infant was exposed to a social stressor (Tronick et al, 1978) to determine the relation between NR3C1 methylation and autonomic nervous system (ANS) reactivity
There were no differences in any of the maternal and infant characteristics between the 23 subjects included and the 102 subjects without heart rate variability (HRV) data that were excluded from this study
Summary
Adversity can result in persistent alterations of an individual’s physiological stress response due, in part, to epigenetic changes. Methylation of the NR3C1 promoter region is associated with increased stress response in infancy as measured by cortisol reactivity (Oberlander et al, 2008; Tyrka et al, 2012; Conradt et al, 2013). Under prolonged conditions of threat and uncertainty, the CAN is hypoactive, disinhibiting the sympathoexcitatory circuits, resulting in a sympathetic response and energy depletion. The lack of this inhibitory mechanism is reflected in deficits such as poor habituation to novel neutral stimuli, a pre-attentive bias for threat information, and poor regulation (Thayer, 2006)
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