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

Kathryn Lester, Susanna Roberts, Robert Keers, Jonathan Coleman, Gerome Breen, Chloe Wong, Xiaohui Xu, Kristian Arendt, Judith Blatter-Meunier, Susan Bögels, Peter Cooper, Cathy Creswell, Einar Heiervang, Chantal Herren, Sanne Hogendoorn, Jennifer Hudson, Karen Krause, Heidi Lyneham, Anna McKinnon, Talia MorrisMaaike Nauta, Ronald Rapee, Yasmin Rey, Silvia Schneider, Sophie Schneider, Wendy Silverman, Patrick Smith, Mikael Thastum, Kerstin Thirlwall, Polly Waite, Gro Janne Wergeland, Thalia Eley

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We previously reported an association between 5HTTLPR genotype and outcome following Cognitive Behaviour 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 (OR=.45, p=.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.
Original languageEnglish
Number of pages7
JournalBritish Journal of Psychiatry
Publication statusPublished - 20 Aug 2015


  • Anxiety
  • Genetics
  • CBT
  • Therapygenetics
  • Treatment response


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