Pharmacoepigenetics of depression: no major influence of MAO-A DNA methylation on treatment response

Katharina Domschke*, Nicola Tidow, Kathrin Schwarte, Christiane Ziegler, Klaus-Peter Lesch, Juergen Deckert, Volker Arolt, Peter Zwanzger, Bernhard T. Baune

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

33 Citations (Web of Science)

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.
Original languageEnglish
Pages (from-to)99-108
JournalJournal of Neural Transmission
Volume122
Issue number1
DOIs
Publication statusPublished - Jan 2015

Keywords

  • Monoamine oxidase A
  • Epigenetics
  • Pharmacoepigenetics
  • Methylation
  • Depression
  • Gender

Cite this