Serotonin transporter gene hypomethylation predicts impaired antidepressant treatment response

Katharina Domschke*, Nicola Tidow, Kathrin Schwarte, Juergen Deckert, Klaus-Peter Lesch, Volker Arolt, Peter Zwanzger, Bernhard T. Baune

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

92 Citations (Web of Science)

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.
Original languageEnglish
Pages (from-to)1167-1176
JournalInternational Journal of Neuropsychopharmacology
Volume17
Issue number8
DOIs
Publication statusPublished - Aug 2014

Keywords

  • Depression
  • epigenetics
  • 5-HTT
  • methylation
  • pharmaco-epigenetics

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