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 = .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. 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.
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 childanxiety 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, NGFrs6330, 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. CONCLUSION: Significant genetic, demographic and clinical predictors of outcome following CBT for anxiety-disorderedchildren 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.
Authors: Jeremy W Pettit; Yasmin Rey; Michele Bechor; Raquel Melendez; Daniella Vaclavik; Victor Buitron; Yair Bar-Haim; Daniel S Pine; Wendy K Silverman Journal: J Anxiety Disord Date: 2017-08-29
Authors: Carly Johnco; Adam B Lewin; Alison Salloum; Tanya K Murphy; Erika A Crawford; Brittney F Dane; Nicole M McBride; Eric A Storch Journal: Child Psychiatry Hum Dev Date: 2016-04
Authors: Jennifer L Hudson; Robert Keers; Susanna Roberts; Jonathan R I Coleman; Gerome Breen; Kristian Arendt; Susan Bögels; Peter Cooper; Cathy Creswell; Catharina Hartman; Einar R Heiervang; Katrin Hötzel; Tina In-Albon; Kristen Lavallee; Heidi J Lyneham; Carla E Marin; Anna McKinnon; Richard Meiser-Stedman; Talia Morris; Maaike Nauta; Ronald M Rapee; Silvia Schneider; Sophie C Schneider; Wendy K Silverman; Mikael Thastum; Kerstin Thirlwall; Polly Waite; Gro Janne Wergeland; Kathryn J Lester; Thalia C Eley Journal: J Am Acad Child Adolesc Psychiatry Date: 2015-04-01 Impact factor: 8.829
Authors: Kathryn J Lester; Susanna Roberts; Robert Keers; Jonathan R I Coleman; Gerome Breen; Chloe C Y Wong; Xiaohui Xu; Kristian Arendt; Judith Blatter-Meunier; Susan Bögels; Peter Cooper; Cathy Creswell; Einar R Heiervang; Chantal Herren; Sanne M Hogendoorn; Jennifer L Hudson; Karen Krause; Heidi J Lyneham; Anna McKinnon; Talia Morris; Maaike H Nauta; Ronald M Rapee; Yasmin Rey; Silvia Schneider; Sophie C Schneider; Wendy K Silverman; Patrick Smith; Mikael Thastum; Kerstin Thirlwall; Polly Waite; Gro Janne Wergeland; Thalia C Eley Journal: Br J Psychiatry Date: 2015-08-20 Impact factor: 9.319