Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents:  The TRAILS study

Lisette J. van der Knaap; Albertine J. Oldehinkel; Frank C. Verhulst; Floor V. A. van Oort; Harriette Riese

doi:10.1016/j.psyneuen.2015.04.012

Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents: The TRAILS study

Lisette J. van der Knaap^*, Albertine J. Oldehinkel, Frank C. Verhulst, Floor V. A. van Oort, Harriette Riese

^*Corresponding author voor dit werk

Interdisciplinair Centrum voor Psychopathologie en Emotieregulatie

Onderzoeksoutput › Academic › peer review

41 Citaten (Scopus)

Samenvatting

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 nnethylation 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. (C) 2015 Elsevier Ltd. All rights reserved.

Originele taal-2	English
Pagina's (van-tot)	46-50
Aantal pagina's	5
Tijdschrift	Psychoneuroendocrinology
Volume	58
DOI's	https://doi.org/10.1016/j.psyneuen.2015.04.012
Status	Published - aug.-2015

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Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents
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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 nnethylation 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. (C) 2015 Elsevier Ltd. All rights reserved.",

keywords = "Cortisol, HPA-axis, Methylation, NR3C1, Epigenetics, Adolescents, CORTISOL RESPONSES, STRESS RESPONSES, ASSOCIATIONS",

author = "{van der Knaap}, {Lisette J.} and Oldehinkel, {Albertine J.} and Verhulst, {Frank C.} and {van Oort}, {Floor V. A.} and Harriette Riese",

year = "2015",

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T2 - The TRAILS study

AU - van der Knaap, Lisette J.

AU - Oldehinkel, Albertine J.

AU - Verhulst, Frank C.

AU - van Oort, Floor V. A.

AU - Riese, Harriette

PY - 2015/8

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N2 - 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 nnethylation 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. (C) 2015 Elsevier Ltd. All rights reserved.

AB - 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 nnethylation 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. (C) 2015 Elsevier Ltd. All rights reserved.

KW - Cortisol

KW - HPA-axis

KW - Methylation

KW - NR3C1

KW - Epigenetics

KW - Adolescents

KW - CORTISOL RESPONSES

KW - STRESS RESPONSES

KW - ASSOCIATIONS

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DO - 10.1016/j.psyneuen.2015.04.012

M3 - Article

SN - 0306-4530

VL - 58

SP - 46

EP - 50

JO - Psychoneuroendocrinology

JF - Psychoneuroendocrinology