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

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; 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

doi:10.1016/j.euroneuro.2021.01.004

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

Eur Neuropsychopharmacol. 2021 Mar:44:105-120. doi: 10.1016/j.euroneuro.2021.01.004. Epub 2021 Jan 20.

Authors

Miriam A Schiele¹, Andreas Reif², Jiaxi Lin³, Georg W Alpers⁴, Evelyn Andersson⁵, Gerhard Andersson⁶, Volker Arolt⁷, Jan Bergström⁸, Per Carlbring⁸, Thalia C Eley⁹, Gabriel Esquivel¹⁰, Tomas Furmark¹¹, Alexander L Gerlach¹², Alfons Hamm¹³, Sylvia Helbig-Lang¹⁴, Jennifer L Hudson¹⁵, Thomas Lang¹⁶, Kathryn J Lester¹⁷, Nils Lindefors¹⁸, Tina B Lonsdorf¹⁹, Paul Pauli²⁰, Jan Richter¹³, Winfried Rief²¹, Susanna Roberts⁹, Christian Rück¹⁸, Koen R J Schruers¹⁰, Christiane Thiel³, Hans-Ulrich Wittchen²², Katharina Domschke²³, Heike Weber²⁴, Ulrike Lueken²⁵

Affiliations

¹ Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: miriam.schiele@uniklinik-freiburg.de.
² Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
³ Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany.
⁵ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Behavioural Sciences and Learning, Division of Psychology, Linköping University, Linköping, Sweden.
⁷ Institute of Translational Psychiatry, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
⁸ Department of Psychology, Stockholm University, Stockholm, Sweden.
⁹ King's College London, Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, United Kingdom.
¹⁰ School for Mental Health and Neuroscience, Maastricht University, The Netherlands and Mondriaan Mental Health Center, Maastricht, The Netherlands.
¹¹ Department of Psychology, Uppsala University, Uppsala, Sweden.
¹² Department of Clinical Psychology and Psychotherapy, University of Cologne, Cologne, Germany.
¹³ Department of Psychology, University of Greifswald, Greifswald, Germany.
¹⁴ Department of Clinical Psychology and Psychotherapy, University of Hamburg, Hamburg, Germany.
¹⁵ Department of Psychology, Centre for Emotional Health, Macquarie University, Sydney, NSW, Australia.
¹⁶ Christoph-Dornier-Foundation for Clinical Psychology, Bremen, Germany; Department of Psychology and Methods, Jacobs University Bremen, Germany.
¹⁷ School of Psychology, University of Sussex, Brighton, United Kingdom.
¹⁸ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Sweden.
¹⁹ Institute for Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²⁰ Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), and Center of Mental Health, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
²¹ Division of Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg, Marburg, Germany.
²² Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
²³ Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, Germany.
²⁴ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany; Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Germany.
²⁵ Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Germany; Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.

PMID: 33483252
DOI: 10.1016/j.euroneuro.2021.01.004

Abstract

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.

Keywords: CBT; Panic disorder; Serotonin transporter gene; Therapy outcome; Therapygenetics; Treatment response.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Anxiety
Anxiety Disorders / genetics
Anxiety Disorders / therapy
Cognitive Behavioral Therapy*
Humans
Serotonin Plasma Membrane Transport Proteins* / genetics

Substances

SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding