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https://hdl.handle.net/2440/96426
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Type: | Journal article |
Title: | Pharmacoepigenetics of depression: no major influence of MAO-A DNA methylation on treatment response |
Author: | Domschke, K. Tidow, N. Schwarte, K. Ziegler, C. Lesch, K. Deckert, J. Arolt, V. Zwanzger, P. Baune, B. |
Citation: | Journal of Neural Transmission, 2015; 122(1):99-108 |
Publisher: | Springer-Verlag |
Issue Date: | 2015 |
ISSN: | 0300-9564 1435-1463 |
Statement of Responsibility: | Katharina Domschke, Nicola Tidow, Kathrin Schwarte, Christiane Ziegler, Klaus-Peter Lesch, Jürgen Deckert, Volker Arolt, Peter Zwanzger, Bernhard T. Baune |
Abstract: | The monoamine oxidase A (MAO-A) gene has been suggested to be involved in the pathogenesis as well as the pharmacological treatment of major depressive disorder. In the present analysis, for the first time a pharmacoepigenetic approach was applied investigating the influence of DNA methylation patterns in the MAO-A regulatory and exon1/intron1 region on antidepressant treatment response. 94 patients of Caucasian descent with major depressive disorder (f = 61; DSM-IV) were analyzed for DNA methylation status at 43 MAO-A CpG sites via direct sequencing of sodium bisulfite treated DNA extracted from blood cells. Patients were also genotyped for the functional MAO-A VNTR. Clinical response to antidepressant treatment with escitalopram was assessed by intra-individual changes of HAM-D-21 scores after 6 weeks of treatment. Apart from two CpG sites, male subjects showed no or only very minor methylation. In female patients, lower methylation at two individual CpG sites in the MAO-A promoter region was nominally associated with impaired response to antidepressant treatment after 6 weeks (GRCh37/hg19: CpG 43.514.063, p = 0.04; CpG 43.514.684, p = 0.009), not, however, withstanding correction for multiple testing. MAO-A VNTR genotypes did not influence MAO-A methylation status. The present pilot data do not suggest a major influence of MAO-A DNA methylation on antidepressant treatment response. However, the presently observed trend towards CpG-specific MAO-A gene hypomethylation-possibly via increased gene expression and consecutively decreased serotonin and/or norepinephrine availability-to potentially drive impaired antidepressant treatment response in female patients might be worthwhile to be followed up in larger pharmacoepigenetic studies. |
Keywords: | Monoamine oxidase A; Epigenetics; Pharmacoepigenetics; Methylation; Depression; Gender |
Description: | First online: 10 May 2014 |
Rights: | © Springer-Verlag Wien 2014 |
DOI: | 10.1007/s00702-014-1227-x |
Published version: | http://dx.doi.org/10.1007/s00702-014-1227-x |
Appears in Collections: | Aurora harvest 7 Psychiatry publications |
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