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

BackgroundWe previously reported an association between 5HTTLPR genotype andoutcome following cognitive–behavioural therapy (CBT) in child anxiety(Cohort 1). Children homozygous for the low-expression short-alleleshowed more positive outcomes. Other similar studies have produced mixedresults, with most reporting no association between genotype and CBToutcome.AimsTo replicate the association between 5HTTLPR and CBT outcome in childanxiety from the Genes for Treatment study (GxT Cohort 2,n = 829).MethodLogistic and linear mixed effects models were used to examine therelationship between 5HTTLPR and CBT outcomes. Mega-analyses using bothcohorts were performed.ResultsThere was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2.Mega-analyses identified a significant association between 5HTTLPR andremission from all anxiety disorders at follow-up (odds ratio 0.45,P = 0.014), but not primary anxiety disorderoutcomes.ConclusionsThe association between 5HTTLPR genotype and CBT outcome did notreplicate. Short-allele homozygotes showed more positive treatmentoutcomes, but with small, non-significant effects. Future studies wouldbenefit from utilising whole genome approaches and large, homogenoussamples.