PMID- 23750220 OWN - NLM STAT- MEDLINE DCOM- 20140929 LR - 20231106 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 6 DP - 2013 TI - Possible associations of NTRK2 polymorphisms with antidepressant treatment outcome: findings from an extended tag SNP approach. PG - e64947 LID - 10.1371/journal.pone.0064947 [doi] LID - e64947 AB - BACKGROUND: Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment. METHODS: We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples. RESULTS: In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects (Pcorr = .018, Pcorr = .015 and Pcorr = .004, respectively). We observed an across-gene BDNF-NTRK2 SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients. CONCLUSIONS/LIMITATIONS: Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies. FAU - Hennings, Johannes M AU - Hennings JM AD - Max-Planck-Institute of Psychiatry, Munich, Germany. hennings@mpipsykl.mpg.de FAU - Kohli, Martin A AU - Kohli MA FAU - Czamara, Darina AU - Czamara D FAU - Giese, Maria AU - Giese M FAU - Eckert, Anne AU - Eckert A FAU - Wolf, Christiane AU - Wolf C FAU - Heck, Angela AU - Heck A FAU - Domschke, Katharina AU - Domschke K FAU - Arolt, Volker AU - Arolt V FAU - Baune, Bernhard T AU - Baune BT FAU - Horstmann, Sonja AU - Horstmann S FAU - Bruckl, Tanja AU - Bruckl T FAU - Klengel, Torsten AU - Klengel T FAU - Menke, Andreas AU - Menke A FAU - Muller-Myhsok, Bertram AU - Muller-Myhsok B FAU - Ising, Marcus AU - Ising M FAU - Uhr, Manfred AU - Uhr M FAU - Lucae, Susanne AU - Lucae S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130604 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 7171WSG8A2 (BDNF protein, human) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Antidepressive Agents/*pharmacology MH - Brain-Derived Neurotrophic Factor/blood MH - *Computational Biology MH - Female MH - Haplotypes MH - Humans MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Receptor, trkB/*genetics MH - Reproducibility of Results MH - Sex Characteristics MH - Treatment Outcome PMC - PMC3672143 COIS- Competing Interests: The authors have the following interests. Arolt is member of advisory boards and/or gave presentations for the following companies: Astra-Zeneca, Janssen-Organon, Eli Lilly, Lundbeck, Pfizer, Servier, and Wyeth. He also received grants from Astra-Zeneca, Lundbeck, and Wyeth. He chaired the committee for the "Wyeth Research Award Depression and Anxiety". Czamara was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy). Domschke has received speaker fees from Pfizer, Lilly and Bristol-Myers Squibb; she is a consultant for Johnson & Johnson and has received funding by Astra Zeneca. Hennings has received travel support to scientific congresses from Eli Lilly, Bayer Vital and Novartis. Menke, Holsboer inventors: Means and methods for diagnosing predisposition for treatment emergent suicidal ideation (TESI). European application number: 08016477.5. International application number: PCT/EP2009/061575. Uhr is patent holder of WO2005/108605A2 and WO2008/151803A2. Katharina Domschke is a PLOS ONE Editorial Board member. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. EDAT- 2013/06/12 06:00 MHDA- 2014/09/30 06:00 PMCR- 2013/06/04 CRDT- 2013/06/11 06:00 PHST- 2012/12/14 00:00 [received] PHST- 2013/04/19 00:00 [accepted] PHST- 2013/06/11 06:00 [entrez] PHST- 2013/06/12 06:00 [pubmed] PHST- 2014/09/30 06:00 [medline] PHST- 2013/06/04 00:00 [pmc-release] AID - PONE-D-12-39669 [pii] AID - 10.1371/journal.pone.0064947 [doi] PST - epublish SO - PLoS One. 2013 Jun 4;8(6):e64947. doi: 10.1371/journal.pone.0064947. Print 2013.