title: Pharmacogenomic predictors of citalopram treatment outcome in major depressive disorder.
abstract: OBJECTIVE
  A significant proportion of patients with major depressive disorder (MDD) do not improve following treatment with first-line antidepressants and, currently, there are no objective indicators of predictors of antidepressant response. The aim of this study was to investigate pre-treatment peripheral gene expression differences between future remitters and non-responders to citalopram treatment and identify potential pharmacogenomic predictors of response.
  
  
  METHODS
  We conducted a gene expression study using Affymetrix HG-U133 Plus2 microarrays in peripheral blood samples from untreated individuals with MDD (N = 77), ascertained at a community outpatient clinic, prior to an 8-week treatment with citalopram. Gene expression differences were assessed between remitters and non-responders to treatment. Technical validation of significant probesets was carried out by qRT-PCR.
  
  
  RESULTS
  A total of 434 probesets displayed significant correlation to change in score and 33 probesests were differentially expressed between eventual remitters and non-responders. Probesets for SMAD 7 (SMA- and MAD-related protein 7) and SIGLECP3 (sialic acid-binding immunoglobulin-like lectin, pseudogene 3) were the most significant differentially expressed genes following FDR correction, and both were down-regulated in individuals who responded to treatment.
  
  
  CONCLUSIONS
  These findings point to SMAD7 and SIGLECP3 as candidate predictive biomarkers of antidepressant response.
authors.affiliation: McGill Group for Suicide Studies, Depressive Disorders Program, Douglas Mental Health University Institute, McGill University , Montreal, Quebec , Canada.
authors.forename: Firoza
authors.initials: F
authors.lastname: Mamdani
authors.forename: Marcelo T
authors.initials: MT
authors.lastname: Berlim
authors.forename: Marie-Martine
authors.initials: MM
authors.lastname: Beaulieu
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods*; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000235:genetics; D051906:Smad7 Protein / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D051906:Smad7 Protein; C497806:SMAD7 protein, human