Pharmacogenomic predictors of citalopram treatment outcome in major depressive disorder

World J Biol Psychiatry. 2014 Feb;15(2):135-44. doi: 10.3109/15622975.2013.766762. Epub 2013 Mar 26.

Abstract

Objectives: 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.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Citalopram / administration & dosage
  • Citalopram / pharmacology*
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / genetics
  • Down-Regulation / genetics
  • Female
  • Gene Expression / genetics*
  • Humans
  • Male
  • Pharmacogenetics / methods*
  • Remission Induction
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / pharmacology*
  • Sialic Acid Binding Immunoglobulin-like Lectins / genetics
  • Smad7 Protein / genetics
  • Treatment Outcome*

Substances

  • Biomarkers
  • SMAD7 protein, human
  • Serotonin Uptake Inhibitors
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • Smad7 Protein
  • Citalopram