Gene expression changes in peripheral mononuclear cells from schizophrenic patients treated with a combination of antipsychotic with fluvoxamine.
Antipsychotic treatment combined with Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant can improve negative symptoms in schizophrenic patients that are unresponsive to antipsychotic drugs alone. The mechanism of this therapeutic effect is not clear. The current study examined molecular changes induced by the combined treatment in human peripheral mononuclear cells (PMC) in order to get insight into its mechanism of action. Gene expression profile of PMC from antipsychotic-treated patients was examined before addition of the SSRI fluvoxamine, and 3 and 6 weeks after. Gene expression patterns screened with a cDNA array, comprising 1176 genes, revealed homologous changes in a range of transcripts related to G-protein coupled receptors (GPCR). Genes related to GPCR-family were assayed using customized cDNA array and the results verified by real-time RT-PCR. The mRNA expression of chemokine receptors, IL8RA and CCR1, and of RGS7 was significantly down-regulated following fluvoxamine augmentation. The clinical assessments showed improvement in negative symptoms following the combined treatment. The transcriptional analysis suggests that the therapeutic mechanism of the combined antipsychotic-fluvoxamine treatment may involve genes associated with G-protein coupled receptors (GPCR). Our findings suggest that gene expression changes in PMC may be useful in investigating the mechanism of drug action in schizophrenia.
Molecular Neuropsychiatry Unit, Shaar Menashe Brain Behavior Laboratory, Shaar Menashe MHC, and Technion -- Faculty of Medicine, Haifa, Israel.
Yael
Y
Chertkow
Orly
O
Weinreb
Moussa B H
MB
Youdim
Henry
H
Silver
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D016666:Fluvoxamine / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D017931:DNA Primers; D018076:DNA, Complementary; D043562:Receptors, G-Protein-Coupled; D012313:RNA; D016666:Fluvoxamine