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Type: Journal article
Title: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Author: Biernacka, J.
Sangkuhl, K.
Jenkins, G.
Whaley, R.
Barman, P.
Batzler, A.
Altman, R.
Arolt, V.
Brockmöller, J.
Chen, C.
Domschke, K.
Hall-Flavin, D.
Hong, C.
Illi, A.
Ji, Y.
Kampman, O.
Kinoshita, T.
Leinonen, E.
Liou, Y.
Mushiroda, T.
et al.
Citation: Translational Psychiatry, 2015; 5(4):e553-1-e553-9
Publisher: Nature
Issue Date: 2015
ISSN: 2158-3188
Statement of
JM Biernacka … BT Baune et. al.
Abstract: Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N=2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P=5.03E-08) and SNPs 5' upstream of the neuregulin-1 gene, NRG1 (P=1.20E-06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.
Keywords: Humans
Protein-Serine-Threonine Kinases
Nerve Tissue Proteins
Transcription Factors
Serotonin Uptake Inhibitors
Antidepressive Agents
Treatment Outcome
Remission Induction
Depressive Disorder, Major
Polymorphism, Single Nucleotide
Middle Aged
Genome-Wide Association Study
Voltage-Gated Sodium Channels
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
DOI: 10.1038/tp.2015.47
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