The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Open accessAbstract
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.
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NRG1 is one such candidate, found here in depression and in a recent meta-analysis of antidepressant response.
“One such candidate is NRG1, identified here in depression, and also in a recent meta-analysis of antidepressant response 50.”
From Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions (2019) · cites this paper as [50]
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Pharmacogenomics and Biomarkers of Depression
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Self-citation
- Authors
- Biernacka, J. M., Sangkuhl, K., Jenkins, G., Whaley, R. M., Barman, P., Batzler, A., Altman, R. B., Arolt, V, Brockmöller, J., Chen, C. H., Domschke, K., Hall-Flavin, D. K., Hong, C. J., Illi, A., Ji, Y., Kampman, O., Kinoshita, T., Leinonen, E., Liou, Y. J., Mushiroda, T., Nonen, S., Skime, M. K., Wang, L., Baune, B. T., Kato, M., Liu, Y. L., Praphanphoj, V, Stingl, J. C., Tsai, S. J., Kubo, M., Klein, T. E., & Weinshilboum, R.
- Affiliations
- Mayo Clinic (US)
- Stanford University (US)
- University of Münster (DE)
- University of Göttingen (DE)
- Taipei Medical University-Shuang Ho Hospital (TW)
- University of Würzburg (DE)
- Taipei Veterans General Hospital (TW)
- University of Tampere (FI)
- Tampere University (FI)
- Kansai Medical University (JP)
- Tampere University Hospital (FI)
- RIKEN Center for Integrative Medical Sciences (JP)
- Hyogo University of Health Sciences (JP)
- The University of Adelaide (AU)
- National Health Research Institutes (TW)
- Ministry of Public Health (TH)
- Federal Institute for Drugs and Medical Devices (DE)
- Corresponding author
- Biernacka, J M
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2015-04-21
- Volume
- 5
- Issue
- 4
- Pages
- e553-e553
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4462610
- OpenAlex
- W2074495846
- Cited by
- 140
- References
- 49
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 8 · 2023: 5 · 2022: 8 · 2021: 15 · 2020: 12 · 2019: 19 · 2018: 22 · 2017: 17 · 2016: 16 · 2015: 3
- FWCI
- 13.82
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-11-01)
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
- GRO (submittedVersion, cc-by)
- Greater South Information System
- Funders
- Thailand Center of Excellence for Life Sciences
- Georgia Clinical and Translational Science Alliance (UL1 RR024150)
- National Science Council (NSC 100-3112-B-400-015, NSC99, NSC 97-2314-B-400-001-MY3 and NSC 100-2314-B-400-002-MY3, NSC 100-2314-B-400-002-MY3, 100-2314-B-400-002-MY3, 100-3112-B-400-015, NSC 97-2314-B- 400-001-MY3, 97-2314-B-400-001-MY3)
- Thailand Research Fund
- National Health Research Institutes (PH-098-PP-46, PH-098-PP-41, PH-098, 99-PP-42, MD-097-PP-14, 99-PP-42, MD-095-PP-02, MD-095-PP-01, PH-098, PH-100-PP-37, 100-SP-11, PH-98, 99, PH-98, PH-098-PP-38)
- SENSHIN Medical Research Foundation
- Tays
- National Center for Genetic Engineering and Biotechnology
- National Institutes of Health (RR024150, GM61374, GM61388)
- Japan Society for the Promotion of Science
- RIKEN
- National Institute of General Medical Sciences (R24GM061374, U19GM061388, R01GM028157, R24 GM6137)
- National Center for Research Resources (RR-024150, UL1RR024150)
- National Center for Advancing Translational Sciences (RR024150)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- selective serotonin reuptake inhibitors, antidepressant response, major depressive disorder, pharmacogenomics, neuregulin-1, genetic susceptibility, candidate genes, meta-analysis, STAR*D, Hamilton Depression Rating Scale
- MeSH terms
- Bromodomain Containing Proteins, Adult, Antidepressive Agents, Cytoskeletal Proteins, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Nerve Tissue Proteins, Pharmacogenetics, Remission Induction, Transcription Factors, Treatment Outcome, Protein Serine-Threonine Kinases, Selective Serotonin Reuptake Inhibitors, Cell Cycle Proteins, Polymorphism, Single Nucleotide, Neuregulin-1, Genome-Wide Association Study, Voltage-Gated Sodium Channels
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