Early life adversity and psychopathology are thought to be linked through HPA-axis deregulation. Changes in methylation levels of stress reactivity genes such as the glucocorticoid receptor gene (NR3C1) can be induced by adversity. Higher NR3C1 methylation levels have been associated with a reduced NR3C1 expression, possibly leading to impaired negative feedback regulation of the HPA-axis. In this study we tested whether methylation levels of NR3C1 were associated with HPA-axis regulation, operationalized as cortisol responses. In 361 adolescents (mean age 16.1, SD=0.6), salivary cortisol samples were collected before, during, and after a social stress task, from which response measures (cortisol activation and recovery) were calculated. Higher NR3C1 methylation levels were associated with a flattened cortisol recovery slope, indicating a delayed recovery time. Cortisol response activation was not associated with NR3C1 methylation. These results suggest that methylation of NR3C1 may impair negative feedback of the HPA-axis in adolescents.

Additional Metadata
Keywords Adolescents, Cortisol, Epigenetics, HPA-axis, Methylation, NR3C1
Persistent URL dx.doi.org/10.1016/j.psyneuen.2015.04.012, hdl.handle.net/1765/80214
Journal Psychoneuroendocrinology
Citation
van der Knaap, L.J, Oldehinkel, A.J, Verhulst, F.C, van Oort, F.V.A, & Riese, H. (2015). Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents. The TRAILS study. Psychoneuroendocrinology, 58, 46–96. doi:10.1016/j.psyneuen.2015.04.012