Identification of a fluoxetine-target network in major depressive disorder

Abstract

Background: While the efficacy of selective serotonin reuptake inhibitor (SSRI) has been widely accepted in major depressive disorder (MDD), mechanisms of the therapeutic action and individual variation in the efficacy remain to be fully elucidated. The purpose of this study was to identify the SSRI-target network that might be relevant to the therapeutic mechanism and the efficacy. Methods: From a public database (Gene Expression Omnibus), we downloaded three transcriptome datasets (GSE43261, GSE54568, and GSE54571). GSE43261 analyzed the transcriptome response of fluoxetine, a SSRI, in dentate gyrus of fluoxetine-responsive and resistant mice model of MDD. GSE54568 and GSE54571 analyzed the transcriptome in dorsolateral prefrontal cortex and anterior cingulate cortex, respectively, of MDD patients. We analyzed these transcriptome datasets using weighted gene co-expression network analysis to identify networks significantly relevant to fluoxetine-responsive MDD mice and MDD patients. Results: We were able to identify three gene co-expression networks significantly relevant to fluoxetine-responsive MDD mice and MDD patients. Comparison of the three networks revealed a common network consisting of 26 genes, including BDNF and RGS4. Both BDNF and RGS4 have been related to the therapeutic effects of SSRI. Conclusions: The gene co-expression network identified in this study may be relevant to the therapeutic mechanism and the efficacy of SSRI.