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
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
收藏
页码:236 / 243
页数:8
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