Abstract
BackgroundHypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress‐related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT).MethodsChildren with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response).ResultsTreatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response.ConclusionsAllele‐specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype‐dependent manner.
Highlights
Hypothalamic–pituitary–adrenal (HPA)axis functioning is known to play an important role in reactivity to stress, and impairments in this system have been widely implicated in psychiatric disorders such as anxiety.[1,2,3] Stress exposure rapidly stimulates glucocorticoid secretion, activating the “fight or flight” response.Termination of this response involves binding of glucocorticoids at the glucocorticoid receptor
GR methylation has been implicated in the development of posttraumatic stress disorder (PTSD) following trauma.[19]. These findings suggest that FKBP5 and GR genetic and epigenetic differences may influence responsiveness to stressful environments, and the development of stressrelated psychiatric disorders
There was no significant effect of FKBP5 or GR genotype on treatment response (Table 2)
Summary
Axis functioning is known to play an important role in reactivity to stress, and impairments in this system have been widely implicated in psychiatric disorders such as anxiety.[1,2,3] Stress exposure rapidly stimulates glucocorticoid secretion, activating the “fight or flight” response. Termination of this response involves binding of glucocorticoids (i.e., cortisol) at the glucocorticoid receptor. Results: Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
