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

Br J Psychiatry. 2016 Feb;208(2):182-8. doi: 10.1192/bjp.bp.114.154997. Epub 2015 Aug 20.

Abstract

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Anxiety Disorders / genetics*
  • Anxiety Disorders / therapy*
  • Child
  • Child, Preschool
  • Cognitive Behavioral Therapy*
  • Female
  • Gene-Environment Interaction*
  • Genotype
  • Humans
  • Male
  • Psychiatric Status Rating Scales
  • Remission Induction
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Treatment Outcome

Substances

  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins