title: Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents. The TRAILS study.
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.
authors.affiliation: Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands. Electronic address: l.j.vanderknaap@erasmusmc.nl.
authors.forename: Lisette J
authors.initials: LJ
authors.lastname: van der Knaap
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Albertine J
authors.initials: AJ
authors.lastname: Oldehinkel
authors.affiliation: Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
authors.affiliation: Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Floor V A
authors.initials: FV
authors.lastname: van Oort
authors.affiliation: Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harriëtte
authors.initials: H
authors.lastname: Riese
mesh_terms: D000293:Adolescent; D019175:DNA Methylation; D025461:Feedback, Physiological / Q000502:physiology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D012463:Saliva / Q000737:chemistry; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone
keywords: Adolescents; Cortisol; Epigenetics; HPA-axis; Methylation; NR3C1