Pharmacogenomic predictors of citalopram treatment outcome in major depressive disorder.
|Title||Pharmacogenomic predictors of citalopram treatment outcome in major depressive disorder.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Mamdani F, Berlim M, Beaulieu M-M, Turecki G|
|Journal||World J Biol Psychiatry|
|Date Published||2014 Feb|
|Keywords||Adult, Biomarkers, Citalopram, Depressive Disorder, Major, Down-Regulation, Female, Gene Expression, Humans, Male, Pharmacogenetics, Remission Induction, Serotonin Uptake Inhibitors, Sialic Acid Binding Immunoglobulin-like Lectins, Smad7 Protein, Treatment Outcome|
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.
|Alternate Journal||World J. Biol. Psychiatry|