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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
Statement of
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
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Psychiatry publications

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