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: Katharina Domschke, Nicola Tidow, Kathrin Schwarte, Christiane Ziegler, Klaus-Peter Lesch, Jürgen Deckert, Volker Arolt, Peter Zwanzger, Bernhard T Baune
• Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 122 Issue 1 Pg. 99-108 (Jan 2015) ISSN: 1435-1463 [Electronic] Austria
• PMID: 24809685 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antidepressive Agents
• Monoamine Oxidase

Topics

• Analysis of Variance
• Antidepressive Agents (therapeutic use)
• Cohort Studies
• DNA Methylation (drug effects, genetics)
• Depressive Disorder, Major (drug therapy, genetics)
• Exons (drug effects, genetics)
• Female
• Genetic Association Studies
• Genotype
• Humans
• Male
• Middle Aged
• Minisatellite Repeats (drug effects, genetics)
• Monoamine Oxidase (genetics)
• Pharmacogenetics
• Treatment Outcome