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

K E Tansey¹, J J H Rucker¹, D H Kavanagh², M Guipponi³, N Perroud⁴, G Bondolfi⁴, E Domenici⁵, D M Evans⁶, J Hauser⁷, N Henigsberg⁸, B Jerman⁹, W Maier¹⁰, O Mors¹¹, M O'Donovan², T J Peters¹², A Placentino¹³, M Rietschel¹⁴, D Souery¹⁵, K J Aitchison¹⁶, I Craig¹, A Farmer¹, J R Wendland¹⁷, A Malafosse¹⁸, G Lewis¹⁹, S Kapur¹, P McGuffin¹, R Uher²⁰

Affiliations

¹ King's College London, Social Genetic and Developmental Psychiatry, Institute of Psychiatry, London, UK.
² MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.
³ Department of Genetic Medicine and Laboratories, University Hospitals of Geneva, Geneva, Switzerland.
⁴ 1] Department of Psychiatry, University of Geneva, Geneva, Switzerland [2] Department of Mental Health and Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.
⁵ F. Hoffmann-La Roche, Pharma Research and Early Development, Basel, Switzerland.
⁶ MRC CAiTE Centre, School of Social and Community Medicine, University of Bristol, Bristol, UK.
⁷ Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
⁸ Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia.
⁹ 1] Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, Ljubljana, Slovenia [2] Institute of Public Health of the Republic of Slovenia, Ljubljana, Slovenia.
¹⁰ Department of Psychiatry, University of Bonn, Bonn, Germany.
¹¹ Research Department P, Aarhus University Hospital, Risskov, Denmark.
¹² School of Clinical Sciences, University of Bristol, Bristol, UK.
¹³ Psychiatric Unit 23, Department of Mental Health, Spedali Civili Hospital and Biological Psychiatry Unit, Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
¹⁴ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
¹⁵ Université Libre de Bruxelles, Erasme Academic Hospital, Department of Psychiatry, Brussels, Belgium.
¹⁶ 1] King's College London, Social Genetic and Developmental Psychiatry, Institute of Psychiatry, London, UK [2] Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.
¹⁷ Worldwide R&D, Pfizer, Cambridge, MA, USA.
¹⁸ 1] Department of Genetic Medicine and Laboratories, University Hospitals of Geneva, Geneva, Switzerland [2] Department of Psychiatry, University of Geneva, Geneva, Switzerland.
¹⁹ School of Social and Community Medicine, University of Bristol, Bristol, UK.
²⁰ 1] King's College London, Social Genetic and Developmental Psychiatry, Institute of Psychiatry, London, UK [2] Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.

PMID: 24445990
DOI: 10.1038/tpj.2013.51

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

K E Tansey et al. Pharmacogenomics J. 2014 Aug.

. 2014 Aug;14(4):395-9.

doi: 10.1038/tpj.2013.51. Epub 2014 Jan 21.

Authors

Affiliations

¹ King's College London, Social Genetic and Developmental Psychiatry, Institute of Psychiatry, London, UK.
² MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.
³ Department of Genetic Medicine and Laboratories, University Hospitals of Geneva, Geneva, Switzerland.
⁴ 1] Department of Psychiatry, University of Geneva, Geneva, Switzerland [2] Department of Mental Health and Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.
⁵ F. Hoffmann-La Roche, Pharma Research and Early Development, Basel, Switzerland.
⁶ MRC CAiTE Centre, School of Social and Community Medicine, University of Bristol, Bristol, UK.
⁷ Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
⁸ Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia.
⁹ 1] Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, Ljubljana, Slovenia [2] Institute of Public Health of the Republic of Slovenia, Ljubljana, Slovenia.
¹⁰ Department of Psychiatry, University of Bonn, Bonn, Germany.
¹¹ Research Department P, Aarhus University Hospital, Risskov, Denmark.
¹² School of Clinical Sciences, University of Bristol, Bristol, UK.
¹³ Psychiatric Unit 23, Department of Mental Health, Spedali Civili Hospital and Biological Psychiatry Unit, Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
¹⁴ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
¹⁵ Université Libre de Bruxelles, Erasme Academic Hospital, Department of Psychiatry, Brussels, Belgium.
¹⁶ 1] King's College London, Social Genetic and Developmental Psychiatry, Institute of Psychiatry, London, UK [2] Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.
¹⁷ Worldwide R&D, Pfizer, Cambridge, MA, USA.
¹⁸ 1] Department of Genetic Medicine and Laboratories, University Hospitals of Geneva, Geneva, Switzerland [2] Department of Psychiatry, University of Geneva, Geneva, Switzerland.
¹⁹ School of Social and Community Medicine, University of Bristol, Bristol, UK.
²⁰ 1] King's College London, Social Genetic and Developmental Psychiatry, Institute of Psychiatry, London, UK [2] Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.

PMID: 24445990
DOI: 10.1038/tpj.2013.51

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

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

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