Correlative gene expression pattern linking RNF123 to cellular stress-senescence genes in patients with depressive disorder: Implication of DRD1 in the cerebral cortex

摘要

Background The expression level of the RNF1213 gene in blood cells has been identified as a disease risk marker, more than ten years before the diagnosis of depression (Glahn et al.; 2012). To explore the status of this gene in the acute depressive state we have quantified the expression of RNF123 in the blood leukocytes (N=17), dorsolateral prefrontal and cingulate cortex (N=24) of patients with diagnosed depression and of matched controls. We have measured the expression of the DRD1 gene as a "neuronal probe". We have also quantified the mRNA of six genes previously identified as markers of the biopsychological stress associated with major depression: FOS, DUSP1, OGG1, STMN1, p16INK4a and TERT. Methods The steady state of mRNA has been quantified by the real-time quantitative PCR technique. Results RNF123 was overexpressed by 45% in the cingulate cortex of patients with psychotic depression. There were distinct co-expression patterns of RNF123 and stress-related genes in the blood cells and brain cortex of patients, demonstrating a transcriptional regulatory shift. In both the prefrontal and cingulate cortex of these patients a strong correlation interlinked STMN1, TERT and DRD1 pointing to a role of these genes in dopamine signaling. Limitations The two groups of patients were clinically heterogeneous. All the patients had received antidepressant treatment, details of which were not available. Conclusion We did not identify RNF123 as a clinically relevant, peripheral state marker of depression, but our study probably lacked statistical power to detect small effect size. It is likely to be involved in distinct pleiotropic molecular pathways at peripheral (blood) and central (brain) level.