Back to Search
Start Over
Pharmacoepigenetics of depression: no major influence of MAO- A DNA methylation on treatment response.
- Source :
- Journal of Neural Transmission; Jan2015, Vol. 122 Issue 1, p99-108, 10p
- Publication Year :
- 2015
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03009564
- Volume :
- 122
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Journal of Neural Transmission
- Publication Type :
- Academic Journal
- Accession number :
- 100208280
- Full Text :
- https://doi.org/10.1007/s00702-014-1227-x