A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to psychological treatments for child anxiety disorders

Keers, Robert, Coleman, Jonathan R. I., Lester, Kathryn J., Roberts, Susanna, Breen, Gerome, Thastum, Mikael, Bögels, Susan, Schneider, Silvia, Heiervang, Einar, Meiser-Stedman, Richard ORCID: https://orcid.org/0000-0002-0262-623X, Nauta, Maaike, Creswell, Cathy, Thirlwall, Kerstin, Rapee, Ronald M., Hudson, Jennifer L., Lewis, Cathryn, Plomin, Robert and Eley, Thalia C. (2016) A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to psychological treatments for child anxiety disorders. Psychotherapy and Psychosomatics, 85 (3). pp. 146-158. ISSN 0033-3190

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Abstract

Background: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to Cognitive Behavioural Therapy (CBT) in children with anxiety disorders. Methods: We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1026 monozygotic (MZ) twin pairs was examined as a function of the pairs’ genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders. Results: The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9%, 55.5% and 41.6% respectively). Conclusions: Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments, but also benefit more from the most intensive types of treatment.

Item Type:	Article
Additional Information:	This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
Uncontrolled Keywords:	differential response,child,anxiety disorders,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Mental Health Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Depositing User:	Pure Connector
Date Deposited:	22 Mar 2016 09:26
Last Modified:	19 Oct 2023 01:37
URI:	https://ueaeprints.uea.ac.uk/id/eprint/57764
DOI:	10.1159/000444023

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