Non-replication of the association between 5HTTLPR and response to psychological therapy for child anxiety disorders

Lester, Kathryn J, Roberts, Susanne, Keers, Roberts, Coleman, Jonathan R I, Breen, Gerome, Wong, Chloe C Y, Xu, Xiaohui, Arendt, Kristian, Blatter-Meunier, Judith, Bögels, Susan, Cooper, Peter, Creswell, Creswell, Heiervang, Einar R., Herren, Chantal, Hogendoorn, Sanne M, Hudson, Jennifer L, Krause, Karen, Lyneham, Heidi J, McKinnon, Anna, Morris, Talia, Nauta, Maaike H, Rapee, Ronald M, Rey, Yasmin, Schneider, Silvia, Schneider, Sophie C, Silverman, Wendy K, Smith, Patrick, Thastum, Mikael, Thirlwall, Kerstin, Waite, Polly, Wergeland, Gro J and Eley, Talia C (2016) Non-replication of the association between 5HTTLPR and response to psychological therapy for child anxiety disorders. British Journal of Psychiatry, 207 (2). pp. 182-188. ISSN 0007-1250

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We previously reported an association between 5HTTLPR genotype and outcome following cognitive–behavioural therapy (CBT) in child anxiety (Cohort 1). Children homozygous for the low-expression short-allele showed more positive outcomes. Other similar studies have produced mixed results, with most reporting no association between genotype and CBT outcome.


To replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2, n = 829).


Logistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed.


There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2. Mega-analyses identified a significant association between 5HTTLPR and remission from all anxiety disorders at follow-up (odds ratio 0.45, P = 0.014), but not primary anxiety disorder outcomes.


The association between 5HTTLPR genotype and CBT outcome did not replicate. Short-allele homozygotes showed more positive treatment outcomes, but with small, non-significant effects. Future studies would benefit from utilising whole genome approaches and large, homogenous samples.

© The Royal College of Psychiatrists 2015.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence.

Item Type: Article
Schools and Departments: School of Psychology > Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology > BF0699 Genetic psychology
Depositing User: Kathryn Lester
Date Deposited: 24 Aug 2015 12:32
Last Modified: 08 Mar 2017 06:10

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