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Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders: A meta-analysis

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Miriam A. Schiele, Andreas Reif, Jiaxi Lin, Georg W. Alpers, Evelyn Andersson, Gerhard Andersson, Volker Arolt, Jan Bergström, Per Carlbring, Thalia C. Eley, Gabriel Esquivel, Tomas Furmark, Alexander L. Gerlach, Alfons Hamm, Sylvia Helbig-Lang, Jennifer L. Hudson, Thomas Lang, Kathryn J. Lester, Nils Lindefors, Tina B. Lonsdorf & 11 more Paul Pauli, Jan Richter, Winfried Rief, Susanna Roberts, Christian Rück, Koen R.J. Schruers, Christiane Thiel, Hans Ulrich Wittchen, Katharina Domschke, Heike Weber, Ulrike Lueken

Original languageEnglish
Pages (from-to)105-120
Number of pages16
JournalEuropean Neuropsychopharmacology
Early online date20 Jan 2021
Accepted/In press10 Jan 2021
E-pub ahead of print20 Jan 2021
PublishedMar 2021

Bibliographical note

Funding Information: This work was supported by the German Research Foundation (DFG) ? Project No. 44541416 ? TRR 58, projects C02 (to KD), C09 (to UL) and Z02 (to AR, KD, PP, TBL and UL), SFB 1193 Z03 (to AR), and the German Ministry of Research and Education (BMBF, 01EE1402F, PROTECT-AD, P5 to KD).This work was partly funded by a grant from the UK Medical Research Council to TC Eley (G0901874).The study is in part funded by the German Federal Ministry of Education and Research (BMBF, 01GV0614) as part of the larger BMBF Psychotherapy Research Funding Initiative Improving the Treatment of Panic Disorder. Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.


King's Authors


There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.

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