Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression

Pharmacometabolomics-informed pharmacogenomics

Y. Ji, S. Hebbring, H. Zhu, G. D. Jenkins, J. Biernacka, K. Snyder, M. Drews, O. Fiehn, Z. Zeng, D. Schaid, D. A. Mrazek, R. Kaddurah-Daouk, R. M. Weinshilboum

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

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 (STARD) 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.

Original languageEnglish (US)
Pages (from-to)97-104
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume89
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Glycine Dehydrogenase
Citalopram
Pharmacogenetics
Serotonin Uptake Inhibitors
Glycine
Single Nucleotide Polymorphism
Major Depressive Disorder
Biomarkers
Depression
Metabolomics
DNA
Genes
Psychiatry
Therapeutics
Phenotype
Enzymes
Research
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression : Pharmacometabolomics-informed pharmacogenomics. / Ji, Y.; Hebbring, S.; Zhu, H.; Jenkins, G. D.; Biernacka, J.; Snyder, K.; Drews, M.; Fiehn, O.; Zeng, Z.; Schaid, D.; Mrazek, D. A.; Kaddurah-Daouk, R.; Weinshilboum, R. M.

In: Clinical Pharmacology and Therapeutics, Vol. 89, No. 1, 01.2011, p. 97-104.

Research output: Contribution to journalArticle

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 2011, 'Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: Pharmacometabolomics-informed pharmacogenomics', Clinical Pharmacology and Therapeutics, vol. 89, no. 1, pp. 97-104. https://doi.org/10.1038/clpt.2010.250
Ji, Y. ; Hebbring, S. ; Zhu, H. ; Jenkins, G. D. ; Biernacka, J. ; Snyder, K. ; Drews, M. ; Fiehn, O. ; Zeng, Z. ; Schaid, D. ; Mrazek, D. A. ; Kaddurah-Daouk, R. ; Weinshilboum, R. M. / Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression : Pharmacometabolomics-informed pharmacogenomics. In: Clinical Pharmacology and Therapeutics. 2011 ; Vol. 89, No. 1. pp. 97-104.
@article{81cd6eb79c0142bc81329fdf5ef5f1e8,
title = "Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: Pharmacometabolomics-informed pharmacogenomics",
abstract = "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 (STARD) 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.",
author = "Y. Ji and S. Hebbring and H. Zhu and Jenkins, {G. D.} and J. Biernacka and K. Snyder and M. Drews and O. Fiehn and Z. Zeng and D. Schaid and Mrazek, {D. A.} and R. Kaddurah-Daouk and Weinshilboum, {R. M.}",
year = "2011",
month = "1",
doi = "10.1038/clpt.2010.250",
language = "English (US)",
volume = "89",
pages = "97--104",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression

T2 - Pharmacometabolomics-informed pharmacogenomics

AU - Ji, Y.

AU - Hebbring, S.

AU - Zhu, H.

AU - Jenkins, G. D.

AU - Biernacka, J.

AU - Snyder, K.

AU - Drews, M.

AU - Fiehn, O.

AU - Zeng, Z.

AU - Schaid, D.

AU - Mrazek, D. A.

AU - Kaddurah-Daouk, R.

AU - Weinshilboum, R. M.

PY - 2011/1

Y1 - 2011/1

N2 - 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 (STARD) 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.

AB - 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 (STARD) 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.

UR - http://www.scopus.com/inward/record.url?scp=78650513748&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650513748&partnerID=8YFLogxK

U2 - 10.1038/clpt.2010.250

DO - 10.1038/clpt.2010.250

M3 - Article

VL - 89

SP - 97

EP - 104

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

SN - 0009-9236

IS - 1

ER -