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  • Title: Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents. The TRAILS study.
    Author: van der Knaap LJ, Oldehinkel AJ, Verhulst FC, van Oort FV, Riese H.
    Journal: Psychoneuroendocrinology; 2015 Aug; 58():46-50. PubMed ID: 25951242.
    Abstract:
    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.
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