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

  • Kathryn J. Lester (a1), Susanna Roberts (a2), Robert Keers (a2), Jonathan R. I. Coleman (a2), Gerome Breen (a3), Chloe C. Y. Wong (a2), Xiaohui Xu (a2), Kristian Arendt (a4), Judith Blatter-Meunier (a5), Susan Bögels (a6), Peter Cooper (a7), Cathy Creswell (a8), Einar R. Heiervang (a9), Chantal Herren (a10), Sanne M. Hogendoorn (a11), Jennifer L. Hudson (a12), Karen Krause (a13), Heidi J. Lyneham (a12), Anna McKinnon (a14), Talia Morris (a12), Maaike H. Nauta (a4), Ronald M. Rapee (a12), Yasmin Rey (a15), Silvia Schneider (a13), Sophie C. Schneider (a12), Wendy K. Silverman (a16), Patrick Smith (a17), Mikael Thastum (a18), Kerstin Thirlwall (a8), Polly Waite (a8), Gro Janne Wergeland (a19) and Thalia C. Eley (a2)...
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.

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Copyright
Corresponding author
Thalia C. Eley, SGDP Centre, Institute of Psychiatry, King's College, Box PO80, London SE5 8AF, UK. Email: thalia.eley@kcl.ac.uk
Footnotes
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Joint first authors.

Combined study supported by UK Medical Research Council grant G0901874/1 to Eley. Lester supported by UK Medical Research Council grant (MR/J011762/1) and Jacobs Foundation Young Scholar grant. Keers supported by UK Medical Research Council Population Health fellowship (MR/K021281/1). Individual trials support by Australian Research Council grant DP0878609 to Hudson, Rapee, and Eley; Australian NHMRC grants to Rapee, Hudson, Lyneham, Mihalopolous (1027556), Lyneham, Hudson and Rapee (488505) and Hudson and Rapee (382008); TrygFonden grant (7-10-1391) to Thastum & Esben Hougaard; Edith ogGodtfred Kirk Christiansens Fond grant (21-5675) to Thastum; Swiss National Science Foundation grant (105314-116517) to Schneider, Western Norway Regional Health Authority grants to Odd Havik (911253) and Heiervang (911366); UK Medical Research Council Clinical Fellowship (G0802821) to Richard Meiser-Stedman; NIMH R01 (MH079943) to Silverman; UK NIHR grants to Creswell (PB-PG-0110-21190) and Cooper (PB-PG-0107-12042); UK Medical Research Council Grants to Cooper and Creswell (09-800-17), Thirlwall, Cooper and Creswell (G0802326), Waite, Creswell and Cooper (G1002011), and Creswell (G0601874). Grant 09/800/17 was managed by NIHR on behalf of the MRC-NIHR partnership. UK NIHR grants to Creswell, Cooper, Emma McIntosh & Lucy Willetts (PB-PG-0110-21190) and Cooper, Creswell, Lucy Willetts & Paul Sheffied(PB-PG-0107-12042); This study presents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

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.

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

  • Kathryn J. Lester (a1), Susanna Roberts (a2), Robert Keers (a2), Jonathan R. I. Coleman (a2), Gerome Breen (a3), Chloe C. Y. Wong (a2), Xiaohui Xu (a2), Kristian Arendt (a4), Judith Blatter-Meunier (a5), Susan Bögels (a6), Peter Cooper (a7), Cathy Creswell (a8), Einar R. Heiervang (a9), Chantal Herren (a10), Sanne M. Hogendoorn (a11), Jennifer L. Hudson (a12), Karen Krause (a13), Heidi J. Lyneham (a12), Anna McKinnon (a14), Talia Morris (a12), Maaike H. Nauta (a4), Ronald M. Rapee (a12), Yasmin Rey (a15), Silvia Schneider (a13), Sophie C. Schneider (a12), Wendy K. Silverman (a16), Patrick Smith (a17), Mikael Thastum (a18), Kerstin Thirlwall (a8), Polly Waite (a8), Gro Janne Wergeland (a19) and Thalia C. Eley (a2)...
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