Journal
JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
Volume 54, Issue 10, Pages 1086-1094Publisher
WILEY
DOI: 10.1111/jcpp.12092
Keywords
CBT; GxE; anxiety disorders; child anxiety disorders
Categories
Funding
- ARC [DP0666048]
- Australian NHMRC [382008]
- UK MRC [GU601020]
- UK MRC Clinical Training Fellowship [G0802326]
- UK NIHR RFPB [PBPG019712042]
- UK MRC NIRG [G0901874]
- UK MRC CDA [G120/635]
- UK MRC Clinician Scientist Fellowship [G0601874]
- National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London
- Maudsley NHS Foundation Trust
- King's College London
- MRC [G0601874, G0901874, G120/635, G0802326, G0601020] Funding Source: UKRI
- Medical Research Council [G0601874, 1097140, G0802326, G120/635, G0601020, G0901874] Funding Source: researchfish
- National Institute for Health Research [PB-PG-0107-12042, PB-PG-0110-21190] Funding Source: researchfish
- National Institutes of Health Research (NIHR) [PB-PG-0107-12042, PB-PG-0110-21190] Funding Source: National Institutes of Health Research (NIHR)
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BackgroundWithin a therapeutic gene by environment (GxE) framework, we recently demonstrated that variation in the Serotonin Transporter Promoter Polymorphism; 5HTTLPR and marker rs6330 in Nerve Growth Factor gene; NGF is associated with poorer outcomes following cognitive behaviour therapy (CBT) for child anxiety disorders. The aim of this study was to explore one potential means of extending the translational reach of GxE data in a way that may be clinically informative. We describe a risk-index' approach combining genetic, demographic and clinical data and test its ability to predict diagnostic outcome following CBT in anxious children. MethodDNA and clinical data were collected from 384 children with a primary anxiety disorder undergoing CBT. We tested our risk model in five cross-validation training sets. ResultsIn predicting treatment outcome, six variables had a minimum mean beta value of 0.5:5HTTLPR, NGF rs6330, gender, primary anxiety severity, comorbid mood disorder and comorbid externalising disorder. A risk index (range 0-8) constructed from these variables had moderate a predictive ability (AUC=.62-.69) in this study. Children scoring high on this index (5-8) were approximately three times as likely to retain their primary anxiety disorder at follow-up as compared with those children scoring 2 or less. ConclusionSignificant genetic, demographic and clinical predictors of outcome following CBT for anxiety-disordered children were identified. Combining these predictors within a risk index could be used to identify which children are less likely to be diagnosis-free following CBT alone and require longer or enhanced treatment. The risk-index' approach represents one means of harnessing the translational potential of GxE data.
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