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

Background 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. Aims To replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2, n = 829). Method Logistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed. Results 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. Conclusions 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. Declaration of interest R.M.R., J.L.H. and H.J.L. are authors of the Cool Kids programme, but receive no direct payments. C.C. was joint author of a book used in treatment within the Overcoming trial and P.W. was joint editor for a book on the treatment of obsessive-compulsive disorder and they receive royalties from sales of the books. W.K.S. is an author of the Anxiety Disorders Interview Schedule for Children from which she receives royalties.