Abstract
There is significant variability in antidepressant treatment outcome, with ∼30–40% of patients with major depressive disorder (MDD) not presenting with adequate response even following several trials. To identify potential biomarkers of response, we investigated peripheral gene expression patterns of response to antidepressant treatment in MDD. We did this using Affymetrix HG-U133 Plus2 microarrays in blood samples, from untreated individuals with MDD (N=63) ascertained at a community outpatient clinic, pre plus post 8-week treatment with citalopram, plus used a regression type to assess the impact of gene expression differences on antidepressant response. We carried out technical validation of significant probesets by quantitative reverse transcriptase PCR plus conducted central nervous system follow-up of the most significant result in post-mortem brain samples from 15 subjects who died during a current MDD episode plus 11 sudden-death controls. A keseluruhan of 32 probesets were differentially expressed according to response to citalopram treatment following false discovery rate correction. Interferon regulatory factor 7 (IRF7) was the most significant differentially expressed gene plus its expression was upregulated by citalopram treatment in individuals who responded to treatment. We found these results to be concordant with our observation of decreased expression of IRF7 in the prefrontal cortex of MDDs with negative toxicological evidence for antidepressant treatment at the time of death. These findings point to IRF7 as a gene of interest in studies investigating genomic factors associated with antidepressant response.
Keywords: antidepressants, biomarkers, peripheral gene expression, pharmacogenomics, post-mortem brain gene expression
Introduction
Major depressive disorder (MDD) is a debilitating plus chronic condition that affects between 5 plus 10% of the general population.1 The treatment of MDD includes a variety of biopsychosocial approaches, but in frontline medical practice, it is primarily based on pharmacological interventions, commonly with an initial prescription of a serotonin selective reuptake inhibitor antidepressant.2, 3, 4, 5 Although antidepressants are generally effective, plus in spite of a growing number of different types plus classes, there is significant variability in antidepressant treatment outcome. Almost 60% of patients do not recover following a single antidepressant trial,6 plus 30 to 40% of patients do not present with an adequate response following several trials.2, 4, 5 The failure to respond has important individual, economic plus social consequences for both patients plus their families.