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

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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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.

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Acknowledgments

The present project was supported by the Doktor Robert Pfleger Stiftung and the Deutsche Forschungsgemeinschaft (DFG), SFB-TRR-58, project C02 (to KD, KPL and JD) as well as A05 (to KPL). We gratefully acknowledge the clinical support by Tilmann Roehrs and Jörn Lewin.

Ethical standards

The study was approved by the ethics committee of the University of Muenster, Germany. Written informed consent was obtained from all participating subjects prior to their inclusion in the study, and the study was conducted according to the ethical principles of the Helsinki Declaration.

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Authors and Affiliations

  1. Department of Psychiatry, University of Wuerzburg, Fuechsleinstrasse 15, 97080, Wurzburg, Germany

    Katharina Domschke, Christiane Ziegler & Jürgen Deckert

  2. Department of Psychiatry, University of Muenster, Albert-Schweitzer-Campus 1, Building A9, 48149, Munster, Germany

    Katharina Domschke, Nicola Tidow, Kathrin Schwarte, Volker Arolt & Peter Zwanzger

  3. Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wurzburg, Germany

    Klaus-Peter Lesch

  4. Department of Psychiatry, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, 5005, Australia

    Bernhard T. Baune

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  1. Katharina Domschke
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Domschke, K., Tidow, N., Schwarte, K. et al. Pharmacoepigenetics of depression: no major influence of MAO-A DNA methylation on treatment response. J Neural Transm 122, 99–108 (2015). https://doi.org/10.1007/s00702-014-1227-x

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