Pharmacogenetics of antidepressant response: A polygenic approach

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Judit García-González, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Katherine E Tansey, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom.
  • ,
  • Joanna Hauser, Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
  • ,
  • Neven Henigsberg, Croatian Institute for Brain Research, Medical School, University of Zagreb, Salata 3, 10 000, Zagreb, Croatia.
  • ,
  • Wolfgang Maier, Department of Psychiatry, University of Bonn, Germany.
  • ,
  • Ole Mors
  • Anna Placentino, Biological Psychiatry Unit and Dual Diagnosis Ward, Istituto Di Ricovero e Cura a Carattere Scientifico, Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
  • ,
  • Marcella Rietschel, Central Institute of Mental Health, Division of Genetic Epidemiology in Psychiatry, Square J5, 68159, Mannheim, Germany.
  • ,
  • Daniel Souery, aa Laboratoire de Psychologie Medicale, Centre Européen de Psychologie Medicale , Université Libre de Bruxelles and Psy Pluriel , Brussels , Belgium.
  • ,
  • Tina Žagar, Institute of Public Health of the Republic of Slovenia, Ljubljana, Slovenia.
  • ,
  • Piotr M Czerski, Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
  • ,
  • Borut Jerman, Institute of Public Health of the Republic of Slovenia, Ljubljana, Slovenia; Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, Ljubljana, Slovenia.
  • ,
  • Henriette N Buttenschøn
  • Thomas G Schulze, Central Institute of Mental Health, Division of Genetic Epidemiology in Psychiatry, Square J5, 68159, Mannheim, Germany.
  • ,
  • Astrid Zobel, Department of Psychiatry, University of Bonn, Germany.
  • ,
  • Anne Farmer, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Katherine J Aitchison, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK; Department of Psychiatry and Medical Genetics, University of Alberta, 116 St and 85 Ave, Edmonton, AB, T6G 2R3, Canada.
  • ,
  • Ian Craig, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Peter McGuffin, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Michel Giupponi, Department of Genetic Medicine and Laboratories, University Hospitals of Geneva, Geneva, Switzerland.
  • ,
  • Nader Perroud, Department of Psychiatry, University of Geneva, Geneva, Switzerland.
  • ,
  • Guido Bondolfi, Center of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline Medicines Research Centre, Verona, Italy.
  • ,
  • David J Evans, Medical Research Council CAiTE Centre, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
  • ,
  • Michael O'Donovan, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom.
  • ,
  • Tim J Peters, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
  • ,
  • Jens R Wendland, Pharma Research and Early Development, F. Hoffmann-La Roche, Basel, Switzerland.
  • ,
  • Glyn Lewis, Molecular Psychiatry Laboratory, Division of Psychiatry, University College London
  • ,
  • Shitij Kapur, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Roy Perlis, Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, USA.
  • ,
  • Volker Arolt, Department of Psychiatry, University of Münster, Münster, Germany.
  • ,
  • Katharina Domschke, University of Wuerzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Wuerzburg, Germany.
  • ,
  • Gerome Breen, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Charles Curtis, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Lee Sang-Hyuk, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Carol Kan, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Stephen Newhouse, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Hamel Patel, Department of Psychosis Studies, The Institute of Psychiatry Psychology and Neuroscience, King's College London, United Kingdom
  • ,
  • Bernhard T Baune, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.
  • ,
  • Rudolf Uher, Department of Psychiatry, Dalhousie University, Halifax, Canada.
  • ,
  • Cathryn M. Lewis, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom. Electronic address: Cathryn.lewis@kcl.ac.uk.
  • ,
  • Chiara Fabbri, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
  • ,
  • Major Depressive Disorder Working Group of the Psychiatric Genomic Consortium

BACKGROUND: Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait.

METHODS: Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole sample or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756).

RESULTS: No significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in individual studies or a meta-analysis. Stratifying by antidepressant did not alter the results.

DISCUSSION: We identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response.

Original languageEnglish
JournalProgress in Neuro-Psychopharmacology & Biological Psychiatry
Volume75
Pages (from-to)128-134
Number of pages7
ISSN0278-5846
DOIs
Publication statusPublished - 3 Apr 2017

    Research areas

  • Journal Article

See relations at Aarhus University Citationformats

ID: 112956849