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Depress Anxiety. 2015 Dec;32(12):861-70. doi: 10.1002/da.22430. Epub 2015 Oct 7.

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

Author information

1
MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
2
School of Psychology, University of Sussex, United Kingdom.
3
National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust, United Kingdom.
4
Department of Psychology and Behavioural Sciences, Aarhus University, Aarhus, Denmark.
5
Department of Psychology, University of Basel, Basel, Switzerland.
6
School of Psychology and Clinical Language Sciences, University of Reading, United Kingdom.
7
Department of Psychology, Stellenbosch University, South Africa.
8
Anxiety Disorders Research Network, Haukeland University Hospital, Bergen, Norway.
9
Department of Forensic Psychiatry, University of Basel Psychiatric Clinics, Basel, Switzerland.
10
Department of Child and Adolescent Psychiatry/De Bascule, Academic Medical Centre, Amsterdam, The Netherlands.
11
Centre for Emotional Health, Department of Psychology, Macquarie University, Sydney, Australia.
12
Department of Psychology, Ruhr-Universität Bochum, Bochum, Germany.
13
Department of Clinical Psychology and Experimental Psychopathology, University of Groningen, The Netherlands.
14
Child Anxiety and Phobia Program, Department of Psychology, Florida International University, Miami, USA.
15
Child Study Center, Yale University School of Medicine, New Haven, Connecticut, USA.

Abstract

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.

KEYWORDS:

DNA methylation; FKBP5; HPA axis; anxiety; biological markers; child/adolescent; cognitive behavior therapy; genetics; glucocorticoid receptor; therapygenetics; treatment

PMID:
26647360
PMCID:
PMC4982063
DOI:
10.1002/da.22430
[Indexed for MEDLINE]
Free PMC Article
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