title: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response.
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. The top association result in the meta-analysis of response represents 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.
authors.affiliation: 1] Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA [2] Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Biernacka
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sangkuhl
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: G
authors.initials: G
authors.lastname: Jenkins
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Whaley
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: P
authors.initials: P
authors.lastname: Barman
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Batzler
authors.affiliation: 1] Department of Genetics, Stanford University, Stanford, CA, USA [2] Department of Bioengineering, Stanford University, Stanford, CA, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Altman
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Department of Clinical Pharmacology, University Göttingen, Göttingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Brockmöller
authors.affiliation: Department of Psychiatry, Taipei Medical University-Shuangho Hospital, New Taipei City, Taiwan.
authors.forename: C H
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Domschke
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Hall-Flavin
authors.affiliation: 1] Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan [2] Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: C J
authors.initials: CJ
authors.lastname: Hong
authors.affiliation: Department of Psychiatry, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Illi
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ji
authors.affiliation: 1] Department of Psychiatry, School of Medicine, University of Tampere, Tampere, Finland [2] Department of Psychiatry, Seinäjoki Hospital District, Seinäjoki, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Kampman
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: 1] Department of Psychiatry, School of Medicine, University of Tampere, Tampere, Finland [2] Department of Psychiatry, Tampere University Hospital, Tampere, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Leinonen
authors.affiliation: 1] Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan [2] Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Liou
authors.affiliation: RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mushiroda
authors.affiliation: Department of Pharmacy, Hyogo University of Health Sciences, Hyogo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nonen
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Skime
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
authors.forename: B T
authors.initials: BT
authors.lastname: Baune
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Y L
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Center for Medical Genetics Research, Rajanukul Institute, Department of Mental Health, Ministry of Public Health Bangkok, Bangkok, Thailand.
authors.forename: V
authors.initials: V
authors.lastname: Praphanphoj
authors.affiliation: Research Division Federal Institute for Drugs and Medical Devices, Bonn, Germany.
authors.forename: J C
authors.initials: JC
authors.lastname: Stingl
authors.affiliation: 1] Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan [2] Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: S J
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Klein
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
authors.forename: R
authors.initials: R
authors.lastname: Weinshilboum
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D020890:Neuregulin-1 / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D014157:Transcription Factors; D016896:Treatment Outcome; D061566:Voltage-Gated Sodium Channels / Q000235:genetics; D000092468:Bromodomain Containing Proteins
chemical_list: D000928:Antidepressive Agents; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D017346:Protein Serine-Threonine Kinases; D017367:Selective Serotonin Reuptake Inhibitors; D014157:Transcription Factors; D061566:Voltage-Gated Sodium Channels; C098415:BRD2 protein, human; D000092468:Bromodomain Containing Proteins; C460645:MCPH1 protein, human; C094131:NRG1 protein, human; C503482:SCN7A protein, human; C486409:STK39 protein, human