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

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.

SUBMITTER: Coleman JR

PROVIDER: S-EPMC5007453 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Coleman Jonathan R I JR Lester Kathryn J KJ Keers Robert R Roberts Susanna S Curtis Charles C Arendt Kristian K Bögels Susan S Cooper Peter P Creswell Cathy C Dalgleish Tim T Hartman Catharina A CA Heiervang Einar R ER Hötzel Katrin K Hudson Jennifer L JL In-Albon Tina T Lavallee Kristen K Lyneham Heidi J HJ Marin Carla E CE Meiser-Stedman Richard R Morris Talia T Nauta Maaike H MH Rapee Ronald M RM Schneider Silvia S Schneider Sophie C SC Silverman Wendy K WK Thastum Mikael M Thirlwall Kerstin K Waite Polly P Wergeland Gro Janne GJ Breen Gerome G Eley Thalia C TC

The British journal of psychiatry : the journal of mental science 20160317 3

<h4>Background</h4>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.<h4>Aims</h4>To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).<h4>Method</h4>Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion ...[more]

PMID: 26989097

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Project description:BackgroundSeveral delivery formats of cognitive behaviour therapy (CBT) for child anxiety have been proposed, however, there is little consensus on the optimal delivery format. The primary goal of this study was to investigate the impact of the child's primary anxiety diagnosis on changes in clinical severity (of the primary problem) during individual CBT, group CBT and guided parent-led CBT. The secondary goal was to investigate the impact of the child's primary anxiety diagnosis on rates of remission for the three treatment formats.MethodsA sample of 1,253 children (5-12 years; Mage = 9.3, SD = 1.7) was pooled from CBT trials carried out at 10 sites. Children had a primary diagnosis of generalised anxiety disorder (GAD), social anxiety disorder (SoAD), specific phobia (SP) or separation anxiety disorder (SAD). Children and parents completed a semistructured clinical interview to assess the presence and severity of DSM-IV psychiatric disorders at preintervention, postintervention and follow-up. Linear mixture modelling was used to evaluate the primary research question and logistic modelling was used to investigate the secondary research question.ResultsIn children with primary GAD, SAD or SoAD, there were no significant differences between delivery formats. However, children with primary SP showed significantly larger reductions in clinical severity following individual CBT compared to group CBT and guided parent-led CBT. The results were mirrored in the analysis of remission responses with the exception that individual CBT was no longer superior to group CBT for children with a primary SP. The difference between individual and group was not significant when follow-up data were examined separately.ConclusionsData show there may be greater clinical benefit by allocating children with a primary SP to individual CBT, although future research on cost-effectiveness is needed to determine whether the additional clinical benefits justify the additional resources required.

Dataset Information

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

Publications

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

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