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

• Published in: Journal of Neural Transmission Vol. 122; no. 1; pp. 99 - 108
• Main Authors: Domschke, Katharina, Tidow, Nicola, Schwarte, Kathrin, Ziegler, Christiane, Lesch, Klaus-Peter, Deckert, Jürgen, Arolt, Volker, Zwanzger, Peter, Baune, Bernhard T.
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.01.2015; Springer Nature B.V
• Subjects: Analysis of Variance; Antidepressive Agents - therapeutic use; Cohort Studies; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; DNA Methylation - drug effects; DNA Methylation - genetics; Exons - drug effects; Exons - genetics; Female; Genetic Association Studies; Genotype; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Minisatellite Repeats - drug effects; Minisatellite Repeats - genetics; Monoamine Oxidase - genetics; Neurology; Neurosciences; Pharmacogenetics; Psychiatry; Psychiatry and Preclinical Psychiatric Studies - Original Article; Treatment Outcome; Epigenetics; Depression; Monoamine oxidase A; Gender; Methylation; Pharmacoepigenetics
• ISSN: 0300-9564; 1435-1463; 1435-1463
• DOI: 10.1007/s00702-014-1227-x

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.