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No association between FKBP5 gene methylation and acute and long-term cortisol output

Prior studies identified DNA methylation (DNA(M)) changes in a regulatory region within the FK506 binding protein 5 (FKBP5) gene as a crucial mediator of long-term negative health outcomes following early adversity. A critical mechanism underlying this link, in turn, has been suggested to be epigene...

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Detalles Bibliográficos
Autores principales: Alexander, Nina, Kirschbaum, Clemens, Stalder, Tobias, Muehlhan, Markus, Vogel, Susanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266811/
https://www.ncbi.nlm.nih.gov/pubmed/32488091
http://dx.doi.org/10.1038/s41398-020-0846-2
Descripción
Sumario:Prior studies identified DNA methylation (DNA(M)) changes in a regulatory region within the FK506 binding protein 5 (FKBP5) gene as a crucial mediator of long-term negative health outcomes following early adversity. A critical mechanism underlying this link, in turn, has been suggested to be epigenetically induced dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. The purpose of this study was thus to investigate associations of FKBP5 DNA(M) with both acute and chronic cortisol output. Two hundred adults with differential exposure to childhood trauma (CT) were underwent a laboratory stressor (Trier Social Stress Test) and provided salivary samples for the analysis of acute cortisol stress responses. In addition, hair cortisol concentrations were determined as a valid measure of integrated long-term cortisol levels. Whole blood samples were drawn for DNA(M) analyses of FKBP5 intron 7 via bisulfite pyrosequencing. In contrast to most prior work, only healthy participants were included in order to disentangle the effects of trauma exposure per se from those related to mental disorders. First, our findings did not reveal strong evidence for a robust effect of CT on FKBP5 intron 7 DNA(M) status, even if genetic predisposition (rs1360780 genotype) was taken into account. Second, FKBP5 DNA(M) levels were found to be unrelated to acute cortisol stress reactivity and long-term cortisol concentration in hair. The failure to demonstrate a significant association between CT and FKBP5 DNA(M) in an exclusively healthy sample could be interpreted as suggesting that individuals’ mental health status may be a critical modulator of previously observed effects.