Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Mar;180(2):150-158.
doi: 10.1002/ajmg.b.32650. Epub 2018 Oct 18.

DNA methylation of FKBP5 and response to exposure-based psychological therapy

Susanna Roberts  1 , Robert Keers  1   2 , Gerome Breen  1   3 , Jonathan R I Coleman  1 , Peter Jöhren  4 , Agnieszka Kepa  1 , Kathryn J Lester  1   5 , Jürgen Margraf  6 , Silvia Scheider  6 , Tobias Teismann  6 , André Wannemüller  6 , Thalia C Eley  1 , Chloe C Y Wong  1
Affiliations

DNA methylation of FKBP5 and response to exposure-based psychological therapy

Susanna Roberts et al. Am J Med Genet B Neuropsychiatr Genet. 2019 Mar.

Abstract

Differential DNA methylation of the hypothalamic-pituitary-adrenal axis related gene FKBP5 has recently been shown to be associated with varying response to environmental influences and may play a role in how well people respond to psychological treatments. Participants (n = 111) received exposure-based cognitive behavioural therapy (CBT) for agoraphobia with or without panic disorder, or specific phobias. Percentage DNA methylation levels were measured for the promoter region and intron 7 of FKBP5. The association between percentage reduction in clinical severity and change in DNA methylation was tested using linear mixed models. The effect of genotype (rs1360780) was tested by the inclusion of an interaction term. The association between change in DNA methylation and FKBP5 expression was examined. Change in percentage DNA methylation at one CpG site of intron 7 was associated with percentage reduction in severity (β = -4.26, p = 3.90 × 10-4 ), where a decrease in DNA methylation was associated with greater response to therapy. An interaction was detected between rs1360780 and changes in DNA methylation in the promoter region of FKBP5 on treatment outcome (p = .045) but did not survive correction for multiple testing. Changes in DNA methylation were not associated with FKBP5 expression. Decreasing DNA methylation at one CpG site of intron 7 of FKBP5 was strongly associated with decreasing anxiety severity following exposure-based CBT. In addition, there was suggestive evidence that allele-specific methylation at the promoter region may also be associated with treatment response. The results of this study add to the growing literature demonstrating the role of biological processes such as DNA methylation in response to environmental influences.

Keywords: anxiety; cognitive behavioral therapy; epigenetics; treatment response.

PubMed Disclaimer

Conflict of interest statement

Breen is a consultant in preclinical genetics for Eli Lilly. All other authors declared no financial interests.

Figures

Figure 1
Figure 1
Change in DNA methylation from pre‐ to posttreatment at CpG 5 of intron 7 and percentage reduction in CGI severity at follow‐up. Percentage reduction in CGI severity at follow‐up was significantly associated with change in % DNA methylation from pre‐ to post‐treatment (β = −4.26, p = 3.90E‐04)
Figure 2
Figure 2
Change in DNA methylation at CpG 2 of the promoter region, rs1360780 genotype and percentage reduction in CGI severity. Percentage reduction in CGI severity from pretreatment to follow‐up and change in % DNA methylation from pre to post‐treatment in CC and CT/TT genotype individuals. Those with the risk genotype (CT/TT) showed a nominally significant association between DNA methylation changes and outcome (β = 1.69, p = .007), while no effect was detected in CC carriers (β = −0.36, p = .641)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Appel, K. , Schwahn, C. , Mahler, J. , Schulz, A. , Spitzer, C. , Fenske, K. , … Grabe, H. J. (2011). Moderation of adult depression by a polymorphism in the FKBP5 gene and childhood physical abuse in the general population. Neuropsychopharmacology, 36(10), 1982–1991. - PMC - PubMed
    1. Belsky, J. , Jonassaint, C. , Pluess, M. , Stanton, M. , Brummett, B. , & Williams, R. (2009). Vulnerability genes or plasticity genes. Molecular Psychiatry, 14(8), 746–754. - PMC - PubMed
    1. Binder, E. B. (2009). The role of FKBP5, a co‐chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology, 34(Suppl 1), S186–S195. - PubMed
    1. Binder, E. B. , Bradley, R. G. , Liu, W. , Epstein, M. P. , Deveau, T. C. , Mercer, K. B. , … Ressler, K. J. (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA, 299(11), 1291–1305. - PMC - PubMed
    1. Coleman, J. R. I. , Lester, K. J. , Roberts, S. , Keers, R. , Lee, S. H. , DE Jong, S. , … Eley, T. C. (2016). Separate and combined effects of genetic variants and pre‐treatment whole blood gene expression on response to exposure‐based cognitive behavioural therapy for anxiety disorders. The World Journal of Biological Psychiatry, 1–34. - PubMed

Publication types

MeSH terms

Substances