The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response

Please always quote using this URN: urn:nbn:de:bvb:20-opus-143223
  • 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 percentResponse 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.show moreshow less

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Author: J. M. Biernacka, K. Sangkuhl, G. Jenkins, R. M. Whaley, P. Barman, A. Batzler, R. B. Altman, V. Arolt, J. Brockmöller, C. H. Chen, K. Domschke, D. K. Hall-Flavin, C. J. Hong, A. Illi, Y. Ji, O. Kampman, T. Kinoshita, E. Leinonen, Y. J. Liou, T. Mushiroda, S. Nonen, M. K. Skime, L. Wang, B. T. Baune, M. Kato, Y. L. Liu, V. Praphanphoj, J. C. Stingl, S. J. Tsai, M. Kubo, T. E. Klein, R. Weinshilboum
URN:urn:nbn:de:bvb:20-opus-143223
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Language:English
Parent Title (English):Translational Psychiatry
Year of Completion:2015
Volume:5
Issue:e553
Source:Translational Psychiatry (2015) 5, e553. DOI: 10.1038/tp.2015.47
DOI:https://doi.org/10.1038/tp.2015.47
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Tag:MCPH1; genetic variation; loci; major depressive disorder; metaanalysis; microcephalin 1; neuregulin-1; population; schizophrenia; susceptibility
Release Date:2017/11/03
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International