A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders

Christopher Rayner; Jonathan R I Coleman; Kirstin L Purves; John Hodsoll; Kimberley Goldsmith; Georg W Alpers; Evelyn Andersson; Volker Arolt; Julia Boberg; Susan Bögels; Cathy Creswell; Peter Cooper; Charles Curtis; Jürgen Deckert; Katharina Domschke; Samir El Alaoui; Lydia Fehm; Thomas Fydrich; Alexander L Gerlach; Anja Grocholewski; Kurt Hahlweg; Alfons Hamm; Erik Hedman; Einar R Heiervang; Jennifer L Hudson; Peter Jöhren; Robert Keers; Tilo Kircher; Thomas Lang; Catharina Lavebratt; Sang-Hyuck Lee; Kathryn J Lester; Nils Lindefors; Jürgen Margraf; Maaike Nauta; Christiane A Pané-Farré; Paul Pauli; Ronald M Rapee; Andreas Reif; Winfried Rief; Susanna Roberts; Martin Schalling; Silvia Schneider; Wendy K Silverman; Andreas Ströhle; Tobias Teismann; Mikael Thastum; Andre Wannemüller; Heike Weber; Hans-Ulrich Wittchen; Christiane Wolf; Christian Rück; Gerome Breen; Thalia C Eley

doi:10.1038/s41398-019-0481-y

A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders

Transl Psychiatry. 2019 May 23;9(1):150. doi: 10.1038/s41398-019-0481-y.

Authors

Christopher Rayner¹, Jonathan R I Coleman^{1

2}, Kirstin L Purves¹, John Hodsoll³, Kimberley Goldsmith³, Georg W Alpers⁴, Evelyn Andersson^{5

6}, Volker Arolt⁷, Julia Boberg^{5

6}, Susan Bögels⁸, Cathy Creswell⁹, Peter Cooper⁹, Charles Curtis^{1

2}, Jürgen Deckert¹⁰, Katharina Domschke^{11

12}, Samir El Alaoui^{5

6}, Lydia Fehm¹³, Thomas Fydrich¹³, Alexander L Gerlach¹⁴, Anja Grocholewski¹⁵, Kurt Hahlweg¹⁵, Alfons Hamm¹⁶, Erik Hedman^{5

6}, Einar R Heiervang¹⁷, Jennifer L Hudson¹⁸, Peter Jöhren¹⁹, Robert Keers²⁰, Tilo Kircher²¹, Thomas Lang²², Catharina Lavebratt²³, Sang-Hyuck Lee^{1

2}, Kathryn J Lester^{1

24}, Nils Lindefors^{5

6}, Jürgen Margraf¹⁹, Maaike Nauta²⁵, Christiane A Pané-Farré¹⁶, Paul Pauli²⁶, Ronald M Rapee¹⁸, Andreas Reif²⁷, Winfried Rief²¹, Susanna Roberts²⁸, Martin Schalling²³, Silvia Schneider¹⁹, Wendy K Silverman²⁹, Andreas Ströhle³⁰, Tobias Teismann¹⁹, Mikael Thastum³¹, Andre Wannemüller^{19

32}, Heike Weber¹⁰, Hans-Ulrich Wittchen³³, Christiane Wolf¹⁰, Christian Rück^{5

6}, Gerome Breen^{34

35}, Thalia C Eley^{36

37}

Affiliations

¹ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
² South London and Maudsley NHS Trust, NIHR Biomedical Research Centre for Mental Health, London, UK.
³ Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
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 Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
⁷ Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
⁸ Research Institute Child Development and Education, University of Amsterdam, Amsterdam, The Netherlands.
⁹ School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK.
¹⁰ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University of Würzburg, Würzburg, 97078, Germany.
¹¹ Faculty of Medicine, Department of Psychiatry and Psychotherapy, Medical Center, University of Freiburg, Freiburg, Germany.
¹² Center for NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
¹³ Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁴ Clinical Psychology and Psychotherapy, University of Cologne, Cologne, Germany.
¹⁵ Department of Psychology, University of Braunschweig, Braunschweig, Germany.
¹⁶ Department of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany.
¹⁷ Division of Mental Health and Addiction, Department of Child and Adolescent Psychiatry, Oslo University Hospital, Oslo, Norway.
¹⁸ Centre for Emotional Health, Department of Psychology, Macquarie University, Sydney, Australia.
¹⁹ Mental Health Research and Treatment Center, Ruhr-Universität Bochum, Bochum, Germany.
²⁰ Department of Biological and Experimental Psychology, School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.
²¹ Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
²² Christoph-Dornier-Stiftung für Klinische Psychologie, Institut für Klinische Psychologie und Psychotherapie, Bremen, Germany.
²³ Neurogenetics Unit, Center for Molecular Medicine, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
²⁴ School of Psychology, University of Sussex, Brighton, UK.
²⁵ Department of Clinical Psychology and Experimental Psychopathology, University of Groningen, Groningen, The Netherlands.
²⁶ Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.
²⁷ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
²⁸ Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁹ Child Study Center, Yale University School of Medicine, New Haven, CT, USA.
³⁰ Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
³¹ Department of Psychology and Behavioural Sciences, Aarhus University, Aarhus, Denmark.
³² Dental Clinic Bochum, Bochum, Germany.
³³ Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
³⁴ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. [email protected].
³⁵ South London and Maudsley NHS Trust, NIHR Biomedical Research Centre for Mental Health, London, UK. [email protected].
³⁶ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. [email protected].
³⁷ South London and Maudsley NHS Trust, NIHR Biomedical Research Centre for Mental Health, London, UK. [email protected].

Abstract

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r_g ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h²_SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h²_SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anxiety Disorders / genetics*
Anxiety Disorders / therapy*
Child
Cognitive Behavioral Therapy / statistics & numerical data*
Depressive Disorder, Major / genetics*
Depressive Disorder, Major / therapy*
Genome-Wide Association Study / statistics & numerical data*
Humans
Outcome Assessment, Health Care / statistics & numerical data*

Abstract

Publication types

MeSH terms

Grants and funding