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Copy number variants and therapeutic response to antidepressant medication in major depressive disorder

The Pharmacogenomics Journal volume 14, pages 395–399 (2014)Cite this article

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Abstract

It would be beneficial to find genetic predictors of antidepressant response to help personalise treatment of major depressive disorder (MDD). Rare copy number variants (CNVs) have been implicated in several psychiatric disorders, including MDD, but their role in antidepressant response has yet to be investigated. CNV data were available for 1565 individuals with MDD from the NEWMEDS (Novel Methods leading to New Medications in Depression and Schizophrenia) consortium with prospective data on treatment outcome with either a serotonergic or noradrenergic antidepressant. No association was seen between the presence of CNV (rare or common), the overall number of CNVs or genomic CNV ‘burden’ and antidepressant response. Specific CNVs were nominally associated with antidepressant response, including 15q13.3 duplications and exonic NRXN1 deletions. These were associated with poor response to antidepressants. Overall burden of CNVs is unlikely to contribute to personalising antidepressant treatment. Specific CNVs associated with antidepressant treatment require replication and further study to confirm their role in the therapeutic action of antidepressant.

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Acknowledgements

The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The research leading to these results has received support from the Innovative Medicine Initiative Joint Undertaking (IMI-JU) under Grant agreement no. 115008 of which resources are composed of European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA) in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). EFPIA members Pfizer, Glaxo Smith Kline and F. Hoffmann La-Roche have contributed work and samples to the project presented here. GENDEP was funded by the European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. Lundbeck provided nortriptyline and escitalopram for the GENDEP study. GlaxoSmithKline and the UK National Institute for Health Research of the Department of Health contributed to the funding of the sample collection at the Institute of Psychiatry, London. GENDEP genotyping was funded by a joint grant from the UK Medical Research Council (MRC, UK) and GlaxoSmithKline (G0701420). GenPod was funded by the Medical Research Council (MRC, UK) and supported by the Mental Health Research Network. GODS study was partly supported by external funding provided by the Swiss branches of the following pharmaceutical companies: GlaxoSmithKline, Wyeth-Lederle, Bristol-Myers-Squibb and Sanofi Aventis. RU is supported by the Canada Research Chair program (http://www.chairs-chaires.gc.ca/). JR was supported by a fellowship from the Wellcome Trust (086635).

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Authors and Affiliations

  1. King’s College London, Social Genetic and Developmental Psychiatry, Institute of Psychiatry, London, UK

    K E Tansey, J J H Rucker, K J Aitchison, I Craig, A Farmer, S Kapur, P McGuffin & R Uher

  2. Department of Psychological Medicine and Neurology, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK

    D H Kavanagh & M O'Donovan

  3. Department of Genetic Medicine and Laboratories, University Hospitals of Geneva, Geneva, Switzerland

    M Guipponi & A Malafosse

  4. Department of Psychiatry, University of Geneva, Geneva, Switzerland

    N Perroud, G Bondolfi & A Malafosse

  5. Department of Mental Health and Psychiatry, University Hospitals of Geneva, Geneva, Switzerland

    N Perroud & G Bondolfi

  6. F. Hoffmann-La Roche, Pharma Research and Early Development, Basel, Switzerland

    E Domenici

  7. MRC CAiTE Centre, School of Social and Community Medicine, University of Bristol, Bristol, UK

    D M Evans

  8. Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland

    J Hauser

  9. Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia

    N Henigsberg

  10. Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, Ljubljana, Slovenia

    B Jerman

  11. Institute of Public Health of the Republic of Slovenia, Ljubljana, Slovenia

    B Jerman

  12. Department of Psychiatry, University of Bonn, Bonn, Germany

    W Maier

  13. Research Department P, Aarhus University Hospital, Risskov, Denmark

    O Mors

  14. School of Clinical Sciences, University of Bristol, Bristol, UK

    T J Peters

  15. Department of Mental Health, Psychiatric Unit 23, Spedali Civili Hospital and Biological Psychiatry Unit, Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    A Placentino

  16. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany

    M Rietschel

  17. Department of Psychiatry, Université Libre de Bruxelles, Erasme Academic Hospital, Brussels, Belgium

    D Souery

  18. Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada

    K J Aitchison

  19. Worldwide R&D, Pfizer, Cambridge, MA, USA

    J R Wendland

  20. School of Social and Community Medicine, University of Bristol, Bristol, UK

    G Lewis

  21. Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada

    R Uher

Authors
  1. K E Tansey
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  2. J J H Rucker
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  5. N Perroud
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  6. G Bondolfi
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  7. E Domenici
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  8. D M Evans
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  9. J Hauser
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  10. N Henigsberg
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  12. W Maier
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  13. O Mors
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  14. M O'Donovan
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  15. T J Peters
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  16. A Placentino
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  17. M Rietschel
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  18. D Souery
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  19. K J Aitchison
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  20. I Craig
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  21. A Farmer
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  22. J R Wendland
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  23. A Malafosse
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  24. G Lewis
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  25. S Kapur
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  26. P McGuffin
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  27. R Uher
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Corresponding author

Correspondence to K E Tansey.

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Competing interests

NP received honoraria for participating in expert panels from pharmaceutical companies including Lundbeck. GB is a member of a national advisory board for Bristol-Myer Squibb and Pfizer and has received research funding from GlaxoSmithKline, Wyeth-Lederle, Bristol-Myers-Squibb and Sanofi Aventis. ED is a full-time employee of F. Hoffmann-La Roche. ED was full-time employee of Glaxo-Smith Kline when he undertook work on this study. JRW is a full-time employee of Pfizer. JRW was full-time employee of F. Hoffmann-La Roche when this work began. NH has participated in clinical trials sponsored by pharmaceutical companies, including GlaxoSmithKline and Lundbeck, and received honoraria for participating in expert panels from pharmaceutical companies, including Lundbeck. MO’D’s department received £2000 in lieu of an honorarium to MO’D from Lilly as a result of his participation in sponsored symposia in 2012. Those symposia were unrelated to the contents of this manuscript. DS is a member of a national advisory boards for Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly and Lundbeck. KJA has been on the Advisory Board for the Bristol-Myers Squibb and Otsuka Pharmaceuticals and in addition received consultancy fees, including payment for lectures and educational presentations, from the same company. She was previously a member of various advisory boards, receiving consultancy fees and honoraria, and has received research grants from various companies, including Lundbeck and GlaxoSmithKline. She currently holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. PMG and AF have previously received consultancy fees and honoraria for participating in expert panels from pharmaceutical companies, including Lundbeck and GlaxoSmithKline, but have had no such income in the past 3 years. SK has received research funding from AstraZeneca, Bristol-Myers Squibb and GlaxoSmithKline and has served as consultant and/or speaker for AstraZeneca, Bioline, BMS-Otsuka, Eli Lilly, Janssen, Lundbeck, NeuroSearch, Pfizer, Roche, Servier and Solvay Wyeth. All the other authors declare no conflict of interest.

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Tansey, K., Rucker, J., Kavanagh, D. et al. Copy number variants and therapeutic response to antidepressant medication in major depressive disorder. Pharmacogenomics J 14, 395–399 (2014). https://doi.org/10.1038/tpj.2013.51

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