Pharmacopsychiatry 2009; 42 - A69
DOI: 10.1055/s-0029-1240141

A genome-wide association study points to multiple loci predicting antidepressant treatment outcome in depression

M Ising 1, S Lucae 1, EB Binder 1, T Bettecken 1, M Uhr 1, S Ripke 1, MA Kohli 1, JM Hennings 1, S Horstmann 1, S Kloiber 1, A Menke 1, B Bondy 2, R Rupprecht 2, K Domschke 3 BT Baune 3Further authors:, V Arolt 3, AJ Rush 4 F Holsboer 1and B Müller-Myhsok 1The first two authors contributed equally to the work and are listed in alphabetical order.
  • 1Max Planck Institut of Psychiatry, Munich, Germany
  • 2Department of Psychiatry, Ludwig Maximilians University, Munich, Germany
  • 3Department of Psychiatry, University of Muenster, Muenster, Germany
  • 4Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA

Even though a variety of antidepressant treatments is available, only half of depressed patients achieve full remission of symptoms. Besides clinical characteristics like recurrent episodes, comorbid anxiety disorders, early age at onset of the disease, higher actual age, a long duration of the current episode as well as female gender, genetic factors contribute to the likelihood of a favourable treatment outcome. We performed a genome-wide pharmacogenetic association study in 339 depressed inpatients from the Munich Antidepressant Response Signature (MARS) project as well as in a pooled sample of further 298 German depressed inpatients, all from Caucasian descent. 328 SNPs showing the highest association with treatment outcome were genotyped in a subsample of 844 Caucasians from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study selected according to the same clinical criteria as the initial sample. 46 SNPs could be replicated at a nominal level of significance but did not withstand correction for multiple testing. However, a multi-locus analysis assuming additivity of the investigated SNPs revealed a significant contribution of the number of responses alleles in combination with clinical characteristics with regard to treatment outcome in both samples, MARS and STAR*D.