title: Pharmacoepigenetics of depression: no major influence of MAO-A DNA methylation on treatment response.
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.
authors.affiliation: Department of Psychiatry, University of Wuerzburg, Fuechsleinstrasse 15, 97080, Wurzburg, Germany, Domschke_K@ukw.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
authors.forename: Nicola
authors.initials: N
authors.lastname: Tidow
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schwarte
authors.forename: Christiane
authors.initials: C
authors.lastname: Ziegler
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
mesh_terms: D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D005091:Exons / Q000187:drug effects / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000187:drug effects / Q000235:genetics; D008995:Monoamine Oxidase / Q000235:genetics*; D010597:Pharmacogenetics; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D008995:Monoamine Oxidase