A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression

Ising, Marcus, Lucae, Susanne, Binder, Elisabeth B., Bettecken, Thomas, Uhr, Manfred, Ripke, Stephan, Kohli, Martin A., Hennings, Johannes M., Horstmann, Sonja, Kloiber, Stefan, Menke, Andreas, Bondy, Brigitta, Rupprecht, Rainer, Domschke, Katharina, Baune, Bernhard T., Arolt, Volker, Rush, John, Holsboer, Florian, and Müller -Myhsok, Bertram (2009) A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression. Archives of General Psychiatry, 66 (9). pp. 966-975.

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Abstract

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.

Item ID: 5244
Item Type: Article (Refereed Research - C1)
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ISSN: 1538-3636
Date Deposited: 10 Sep 2009 22:48
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920410 Mental Health @ 100%
Citation Count from Web of Science Web of Science 116
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