Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics.

Journal Article (Clinical Trial;Journal Article)

Major depressive disorder (MDD) is a common psychiatric disease. Selective serotonin reuptake inhibitors (SSRIs) are an important class of drugs used in the treatment of MDD. However, many patients do not respond adequately to SSRI therapy. We used a pharmacometabolomics-informed pharmacogenomic research strategy to identify citalopram/escitalopram treatment outcome biomarkers. Metabolomic assay of plasma samples from 20 escitalopram remitters and 20 nonremitters showed that glycine was negatively associated with treatment outcome (P = 0.0054). This observation was pursued by genotyping tag single-nucleotide polymorphisms (SNPs) for genes encoding glycine synthesis and degradation enzymes, using 529 DNA samples from SSRI-treated MDD patients. The rs10975641 SNP in the glycine dehydrogenase (GLDC) gene was associated with treatment outcome phenotypes. Genotyping for rs10975641 was carried out in 1,245 MDD patients in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, and its presence was significant (P = 0.02) in DNA taken from these patients. These results highlight a possible role for glycine in SSRI response and illustrate the use of pharmacometabolomics to "inform" pharmacogenomics.

Full Text

Duke Authors

Cited Authors

  • Ji, Y; Hebbring, S; Zhu, H; Jenkins, GD; Biernacka, J; Snyder, K; Drews, M; Fiehn, O; Zeng, Z; Schaid, D; Mrazek, DA; Kaddurah-Daouk, R; Weinshilboum, RM

Published Date

  • January 2011

Published In

Volume / Issue

  • 89 / 1

Start / End Page

  • 97 - 104

PubMed ID

  • 21107318

Pubmed Central ID

  • PMC3034442

Electronic International Standard Serial Number (EISSN)

  • 1532-6535

Digital Object Identifier (DOI)

  • 10.1038/clpt.2010.250


  • eng

Conference Location

  • United States