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Br J Psychiatry. 2016 Sep;209(3):236-43. doi: 10.1192/bjp.bp.115.168229. Epub 2016 Mar 17.

Genome-wide association study of response to cognitive-behavioural therapy in children with anxiety disorders.

Author information

1
Jonathan R. I. Coleman, MSc, King's College London, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, UK; Kathryn J. Lester, DPhil, King's College London, IoPPN, MRC SGDP Centre, UK, and School of Psychology, University of Sussex, UK; Robert Keers, PhD, Susanna Roberts, MSc, King's College London, IoPPN, MRC SGDP Centre, UK; Charles Curtis, MSc, King's College London, IoPPN, MRC SGDP Centre, UK, and National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust, UK; Kristian Arendt, PhD, Department of Psychology and Behavioural Sciences, Aarhus University, Denmark; Susan Bögels, PhD, Research Institute Child Development and Education, University of Amsterdam, The Netherlands; Peter Cooper, DPhil, School of Psychology and Clinical Language Sciences, University of Reading, UK, and Department of Psychology, Stellenbosch University, South Africa; Cathy Creswell, DClinPsy, PhD, School of Psychology and Clinical Language Sciences, University of Reading, UK; Tim Dalgleish, PhD, MRC Cognition & Brain Sciences Unit, Cambridge, UK; Catharina A. Hartman, PhD, Department of Psychiatry, University of Groningen, University Medical Center Groningen, The Netherlands; Einar R. Heiervang, PhD, Institute of Clinical Medicine, University of Oslo, Norway; Katrin Hötzel, PhD, Department of Psychology, Ruhr-Universität Bochum, Germany; Jennifer L. Hudson, PhD, Centre for Emotional Health, Department of Psychology, Macquarie University, Sydney, Australia; Tina In-Albon, PhD, Clinical Child and Adolescent Psychology, Universität Koblenz-Landau, Germany; Kristen Lavallee, PhD, Department of Psychology, University of Basel, Switzerland; Heidi J. Lyneham, PhD, Centre for Emotional Health, Department of Psychology, Macquarie University, Sydney, Australia; Carla E. Marin, PhD, Yale University, Child Study Center, New Haven, Connecticut, USA; Richard Meiser-S

Abstract

BACKGROUND:

Anxiety disorders are common, and cognitive-behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.

AIMS:

To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).

METHOD:

Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.

RESULTS:

No variants passed a genome-wide significance threshold (P = 5 × 10(-8)) in either analysis. Four variants met criteria for suggestive significance (P<5 × 10(-6)) in association with response post-treatment, and three variants in the 6-month follow-up analysis.

CONCLUSIONS:

This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.

PMID:
26989097
PMCID:
PMC5007453
DOI:
10.1192/bjp.bp.115.168229
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Declaration of interest R.M.R., J.L.H. and H.J.L. are co-authors of the Cool Kids program but receive no direct payments. C. Creswell is co-author of books in the ’Overcoming’ series and receives royalties. W.K.S. is author of the Anxiety Disorders Interview Schedule for Children and receives royalties. G.B. is a consultant in pre-clinical genetics for Eli Lilly.

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