Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/93952
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Serotonin transporter gene hypomethylation predicts impaired antidepressant treatment response |
Author: | Domschke, K. Tidow, N. Schwarte, K. Deckert, J. Lesch, K. Arolt, V. Zwanzger, P. Baune, B. |
Citation: | International Journal of Neuropsychopharmacology, 2014; 17(8):1167-1176 |
Publisher: | Cambridge University Press |
Issue Date: | 2014 |
ISSN: | 1461-1457 1469-5111 |
Statement of Responsibility: | Katharina Domschke, Nicola Tidow, Kathrin Schwarte, Jürgen Deckert, Klaus-Peter Lesch, Volker Arolt, Peter Zwanzger and Bernhard T. Baune |
Abstract: | Variation in the serotonin transporter gene (5-HTT; SERT; SLC6A4) has been suggested to pharmacogenetically drive interindividual differences in antidepressant treatment response. In the present analysis, a 'pharmaco-epigenetic' approach was applied by investigating the influence of DNA methylation patterns in the 5-HTT transcriptional control region on antidepressant treatment response. Ninety-four patients of Caucasian descent with major depressive disorder (MDD) (f = 61) were analysed for DNA methylation status at nine CpG sites in the 5-HTT transcriptional control region upstream of exon 1A via direct sequencing of sodium bisulfite treated DNA extracted from blood cells. Patients were also genotyped for the functional 5-HTTLPR/rs25531 polymorphisms. Clinical response to treatment with escitalopram was assessed by intra-individual changes of HAM-D-21 scores after 6 wk of treatment. Lower average 5-HTT methylation across all nine CpGs was found to be associated with impaired antidepressant treatment response after 6 wk (p = 0.005). This effect was particularly conferred by one individual 5-HTT CpG site (CpG2 (GRCh37 build, NC_000017.10 28.563.102; p = 0.002). 5-HTTLPR/rs25531 haplotype was neither associated with 5-HTT DNA methylation nor treatment response. This analysis suggests that DNA hypomethylation of the 5-HTT transcriptional control region - possibly via increased serotonin transporter expression and consecutively decreased serotonin availability - might impair antidepressant treatment response in Caucasian patients with MDD. This pharmaco-epigenetic approach could eventually aid in establishing epigenetic biomarkers of treatment response and thereby a more personalized treatment of MDD. |
Keywords: | Depression; epigenetics; 5-HTT; methylation; pharmaco-epigenetics |
Rights: | © CINP 2014 |
DOI: | 10.1017/S146114571400039X |
Grant ID: | C02 A05 |
Published version: | http://dx.doi.org/10.1017/s146114571400039x |
Appears in Collections: | Aurora harvest 7 Medicine publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_93952.pdf | Published version | 320.76 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.