HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS

• Published in: Depression and anxiety Vol. 32; no. 12; pp. 861 - 870
• Main Authors: Roberts, Susanna, Keers, Robert, Lester, Kathryn J, Coleman, Jonathan R. I., Breen, Gerome, Arendt, Kristian, Blatter-Meunier, Judith, Cooper, Peter, Creswell, Cathy, Fjermestad, Krister, Havik, Odd E., Herren, Chantal, Hogendoorn, Sanne M., Hudson, Jennifer L., Krause, Karen, Lyneham, Heidi J., Morris, Talia, Nauta, Maaike, Rapee, Ronald M., Rey, Yasmin, Schneider, Silvia, Schneider, Sophie C., Silverman, Wendy K., Thastum, Mikael, Thirlwall, Kerstin, Waite, Polly, Eley, Thalia C., Wong, Chloe C. Y.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-12-2015; Hindawi Limited; John Wiley and Sons Inc
• Subjects: Adolescent; Alleles; Anxiety; Anxiety Disorders - genetics; Anxiety Disorders - therapy; biological markers; Child; Child, Preschool; child/adolescent; Cognition & reasoning; cognitive behavior therapy; Cognitive Behavioral Therapy; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - genetics; Epigenesis, Genetic - genetics; Epigenetics; Epigenomics; Female; FKBP5; Genes; Genetics; glucocorticoid receptor; HPA axis; Humans; Hypothalamo-Hypophyseal System - physiopathology; Male; Pituitary-Adrenal System - physiopathology; Polymorphism, Single Nucleotide; Receptors, Glucocorticoid - genetics; Studies; Tacrolimus Binding Proteins - genetics; therapygenetics; treatment; Treatment Outcome; anxiety; treatment; child/adolescent; glucocorticoid receptor; genetics; cognitive behavior therapy; DNA methylation; biological markers; HPA axis; therapygenetics; FKBP5
• ISSN: 1091-4269; 1520-6394
• DOI: 10.1002/da.22430

Background
Hypothalamic–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).
Methods
Children 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).
Results
Treatment 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.
Conclusions
Allele‐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.