 |
|
A Genomewide Association Study Points to Multiple Loci That Predict Antidepressant Drug Treatment Outcome in Depression
Marcus Ising, PhD*;
Susanne Lucae, MD, PhD*;
Elisabeth B. Binder, MD, PhD;
Thomas Bettecken, MD;
Manfred Uhr, MD, PhD;
Stephan Ripke, MD;
Martin A. Kohli, MSc;
Johannes M. Hennings, MD;
Sonja Horstmann, MD;
Stefan Kloiber, MD;
Andreas Menke, MD;
Brigitta Bondy, MD;
Rainer Rupprecht, MD;
Katharina Domschke, MD, MA;
Bernhard T. Baune, MD, PhD, MPH;
Volker Arolt, MD;
A. John Rush, MD;
Florian Holsboer, MD, PhD;
Bertram Müller-Myhsok, MD
Arch Gen Psychiatry. 2009;66(9):966-975.
Context The efficacy of antidepressant drug treatment in depression is unsatisfactory; 1 in 3 patients does not fully recover even after several treatment trials. Genetic factors and clinical characteristics contribute to the failure of a favorable treatment outcome.
Objective To identify genetic and clinical determinants of antidepressant drug treatment outcome in depression.
Design Genomewide pharmacogenetic association study with 2 independent replication samples.
Setting We performed a genomewide association study in patients from the Munich Antidepressant Response Signature (MARS) project and in pooled DNA from an independent German replication sample. A set of 328 single-nucleotide polymorphisms highly related to outcome in both genomewide association studies was genotyped in a sample of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.
Participants A total of 339 inpatients with a depressive episode (MARS sample), a further 361 inpatients with depression (German replication sample), and 832 outpatients with major depression (STAR*D sample).
Main Outcome Measures We generated a multilocus genetic variable that described the individual number of alleles of the selected single nucleotide polymorphisms associated with beneficial treatment outcome in the MARS sample ("response" alleles) to evaluate additive genetic effects on antidepressant drug treatment outcome.
Results Multilocus analysis revealed a significant contribution of a binary variable that categorized patients as carriers of a high vs low number of response alleles in the prediction of antidepressant drug treatment outcome in both samples (MARS and STAR*D). In addition, we observed that patients with a comorbid anxiety disorder combined with a low number of response alleles showed the least favorable outcome.
Conclusion These results demonstrate the importance of multiple genetic factors combined with clinical features in the prediction of antidepressant drug treatment outcome, which underscores the multifactorial nature of this trait.
Author Affiliations: Max Planck Institute of Psychiatry, Munich, Germany (Drs Ising, Lucae, Binder, Bettecken, Uhr, Ripke, Hennings, Horstmann, Kloiber, Menke, Holsboer, and Müller-Myhsok and Mr Kohli); Department of Psychiatry, Ludwig Maximilians University, Munich (Drs Bondy and Rupprecht); Department of Psychiatry, Westfalian Wilhelms University, Muenster, Germany (Drs Domschke, Baune, and Arolt); Department of Psychiatry, James Cook University, Townsville, Australia (Dr Baune); Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Dr Rush); and Department of Clinical Sciences, Duke–National University of Singapore (Dr Rush).
*Drs Ising and Lucae contributed equally to this article; their names are listed in alphabetical order.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
This Month in Archives of General Psychiatry
Arch Gen Psychiatry. 2009;66(9):929.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
A Step Toward Personalized Treatment of Depression
JWatch Psychiatry 2009;2009:3-3.
FULL TEXT
|
