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

Abstract

BackgroundWe 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.AimsTo replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2, n = 829).MethodLogistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed.ResultsThere 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.ConclusionsThe 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.

A Longitudinal Twin and Sibling Study of Associations between Insomnia and Depression Symptoms in Young Adults

“…We have been studying genetic influences on outcome following psychological therapy in anxiety disorders. As with any area of psychiatric genetics, the work requires large sample sizes and most studies to date have been underpowered (e.g., work on pediatric anxiety 48 ). However there are preliminary indications that there are genetic influences on response to psychological treatment, 49 indicating that this is a fruitful avenue for further research.…”

Annual Research Review: An expanded account of information‐processing mechanisms in risk for child and adolescent anxiety and depression

“…The magnitude of genetic effects on symptoms may increase with age (Waszczuk, Zavos, Gregory, & Eley, ); ‘new’ sources of genetic influence may emerge at particular time points across adolescence (Waszczuk, Zavos, Gregory, & Eley, ); and finally, there may be shared genetic variance between anxiety and depression in youth (Waszczuk et al., ). Studies uncovering which genes are involved have revealed inconsistent findings with many candidate–gene association studies being unable to replicate initially promising associations between specific gene polymorphisms and behaviours, and more hypothesis‐free genome‐wide association studies failing to find associations that meet genome‐wide level significance (Lester et al., ; Trzaskowski et al., ). Despite these uncertain results, there have nonetheless been efforts to investigate how genetic vulnerability is expressed through more intermediate mechanisms to influence symptoms.…”

Hpa Axis Related Genes and Response to Psychological Therapies: Genetics and Epigenetics

“…All participants come from the Genes for Treatment (GxT) Study, an international multisite collaboration designed to identify predictors of outcome following CBT for child anxiety. [28,36]…”

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