Mild daily stress, in interaction with NR3C1 DNA methylation levels, is linked to alterations in the HPA axis and ANS response to acute stress in early adolescents.

Background: Daily Hassles (DH) or daily stress - is a mild type of stressor with unique contributions to psychological distress. Yet, most prior studies that investigate the effects of stressful life experiences focus on childhood trauma or on early life stress and little is known about the effects of DH on epigenetic changes in stress system related genes and on the physiological response to social stressors.

Methods: In the present study, conducted among 101 early adolescents (mean age = 11.61; SD = 0.64), we investigated whether Autonomic Nervous System (ANS) (namely heart rate and heart rate variability) and Hypothalamic-Pituitary-Adrenal (HPA) axis functioning (measured as cortisol stress reactivity and recovery) are associated with DNA methylation (DNAm) in the glucocorticoid receptor gene (NR3C1), the level of DH and their interaction. To assess the stress system functioning the TSST protocol was used.

Results: Our findings show that higher NR3C1 DNAm in interaction with higher levels of daily hassles, is associated with blunted HPA axis reactivity to psychosocial stress. In addition, higher levels of DH are associated with extended HPA axis stress recovery. In addition, participants with higher NR3C1 DNAm had lower ANS adaptability to stress, specifically lower parasympathetic withdrawal; for heart rate variability this effect was strongest for participants with higher level of DH.

Conclusions: The observation that interaction effects between NR3C1 DNAm levels and daily stress on the functioning of the stress-systems, are already detectable in young adolescents, highlights the importance of early interventions, not only in the case of trauma, but also daily stress. This might help to prevent stress-induced mental and physical disorders later in life.