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Non-replication of the association between 5HTTLPR and response to psychological therapy for child anxiety disorders
Kathryn J Lester1, Susanna Roberts1, Robert Keers1
1Kathryn J. Lester, DPhil, School of Psychology, University of Sussex, and King's College London, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK; Susanna Roberts, MSc, King's College London, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK; Robert Keers, PhD, King's College London, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK; Jonathan R. I. Coleman, MSc, King's College London, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK; Gerome Breen, PhD, King's College London, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK and National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust, UK; Chloe C. Y. Wong, PhD, King's College London, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK; Xiaohui Xu, MD, King's College London, MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK; Kristian Arendt, MSc, Department of Clinical Psychology and Experimental Psychopathology, University of Groningen, The Netherlands; Judith Blatter-Meunier, PhD, Department of Psychology, University of Basel, Basel, Switzerland; Susan Bögels, PhD, Research Institute Child Development and Education, University of Amsterdam, The Netherlands; Peter Cooper, DPhil, School of Psychology and Clinical Language Sciences, University of Reading, UK and Department of Psychology, Stellenbosch University, South Africa; Cathy Creswell, DClinPsy, PhD, School of Psychology and Clinical Language Sciences, U
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.
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