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

被引：31

作者：

Coleman, Jonathan R. I. ^{[1
]}

Lester, Kathryn J. ^{[1
,2
]}

Keers, Robert ^{[1
]}

Roberts, Susanna ^{[1
]}

Curtis, Charles ^{[1
,3
]}

Arendt, Kristian ^{[4
]}

Bogels, Susan ^{[5
]}

Cooper, Peter ^{[6
,7
]}

Creswell, Cathy ^{[6
]}

Dalgleish, Tim ^{[8
]}

Hartman, Catharina A. ^{[9
]}

Heiervang, Einar R. ^{[10
]}

Hoetzel, Katrin ^{[11
]}

Hudson, Jennifer L. ^{[12
]}

In-Albon, Tina ^{[13
]}

Lavallee, Kristen ^{[14
]}

Lyneham, Heidi J. ^{[12
]}

Marin, Carla E. ^{[15
]}

Meiser-Stedman, Richard ^{[16
]}

Morris, Talia ^{[12
]}

Nauta, Maaike H. ^{[17
]}

Rapee, Ronald M. ^{[12
]}

Schneider, Silvia ^{[11
]}

Schneider, Sophie C. ^{[12
]}

Silverman, Wendy K. ^{[15
]}

Thastum, Mikael ^{[4
]}

Thirlwall, Kerstin ^{[6
]}

Waite, Polly ^{[6
]}

Wergeland, Gro Janne ^{[18
,19
]}

Breen, Gerome ^{[1
,3
]}

Eley, Thalia C. ^{[1
]}

机构：

[1] Kings Coll London, IoPPN, MRC SGDP Ctr, London WC2R 2LS, England

[2] Univ Sussex, Sch Psychol, Brighton BN1 9RH, E Sussex, England

[3] South London & Maudsley Natl Hlth Serv Trust, Natl Inst Hlth Res Biomed Res Ctr, London, England

[4] Aarhus Univ, Dept Psychol & Behav Sci, DK-8000 Aarhus C, Denmark

[5] Univ Amsterdam, Res Inst Child Dev & Educ, NL-1012 WX Amsterdam, Netherlands

[6] Univ Reading, Sch Psychol & Clin Language Sci, Reading RG6 2AH, Berks, England

[7] Univ Stellenbosch, Dept Psychol, ZA-7600 Stellenbosch, South Africa

[8] MRC Cognit Brain Sci Unit, Cambridge, England

[9] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9700 AB Groningen, Netherlands

[10] Univ Oslo, Inst Clin Med, N-0316 Oslo, Norway

[11] Ruhr Univ Bochum, Dept Psychol, Bochum, Germany

[12] Macquarie Univ, Dept Psychol, Ctr Emot Hlth, Sydney, NSW, Australia

[13] Univ Koblenz Landau, Clin Child & Adolescent Psychol, Mainz, Germany

[14] Univ Basel, Dept Psychol, CH-4003 Basel, Switzerland

[15] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA

[16] MRC Cognit & Brain Sci Unit, Cambridge, England

[17] Univ Groningen, Dept Clin Psychol & Expt Psychopathol, NL-9700 AB Groningen, Netherlands

[18] Haukeland Hosp, Dept Child & Adolescent Psychiat, Bergen, Norway

[19] Haukeland Hosp, Anxiety Disorders Res Network, Bergen, Norway

来源：

BRITISH JOURNAL OF PSYCHIATRY | 2016年 / 209卷 / 03期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会; 瑞士国家科学基金会; 澳大利亚研究理事会; 美国国家卫生研究院;

关键词：

PANIC DISORDER; METAANALYSIS; REPLICATION; PREDICTORS; VARIANTS; LINKAGE; PLINK; WILL; LOCI; PTSD;

D O I：

10.1192/bjp.bp.115.168229

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

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 IIlumina 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 x 10(-8)) in either analysis. Four variants met criteria for suggestive significance (P < 5 x 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.

引用

页码：236 / 243

页数：8

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