Predicting Outcomes Following Cognitive Behaviour Therapy in Child Anxiety Disorders: The Influence of Genetic, Demographic and Clinical Information

Background: Within a therapeutic gene by environment (G × E) 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 G × E 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. Method: DNA 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. Results: In 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 = 0.62-0.69) 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. Conclusion: Significant 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 G × E data.