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A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder.

ABSTRACT: Gene expression in peripheral blood has the potential to inform on pathophysiological mechanisms and has emerged as a viable avenue for the identification of biomarkers. Here, we aimed to identify gene expression candidate genes and to explore the potential for a composite gene expression measure as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6-12-month period and in 40 age- and gender-matched healthy control subjects. Second, a composite gene expression measure was constructed in the first half study sample and independently validated in the second half of the sample. We found downregulation of POLG and OGG1 expression in bipolar disorder patients compared with healthy control subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the receiver-operating characteristic curve of 0.81 (P < 0.0001) in sample 1, which was replicated with a value of 0.73 (P < 0.0001) in sample 2, corresponding with a moderately accurate test. The present findings of altered POLG, OGG1 and NDUFV2 expression point to disturbances within mitochondrial function and DNA repair mechanisms in bipolar disorder. Further, a composite gene expression measure could hold promise as a potential diagnostic biomarker.

SUBMITTER: Munkholm K

PROVIDER: S-EPMC4564565 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder.

Munkholm K K Peijs L L Vinberg M M Kessing L V LV

Translational psychiatry 20150804

Gene expression in peripheral blood has the potential to inform on pathophysiological mechanisms and has emerged as a viable avenue for the identification of biomarkers. Here, we aimed to identify gene expression candidate genes and to explore the potential for a composite gene expression measure as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patien ...[more]

PMID: 26241352

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Project description:IntroductionAlthough major depressive diroder (MDD) has brought huge burden and challenges to society globally, effective and accurate diagnoses and treatments remain inadequate. The pathogenesis that for women are more likely to suffer from depression than men needs to be excavated as well. The function of circRNAs in pathological process of depression has not been widely investigated. This study aims to explore potential diagnostic biomarker circRNA of female patients with MDD and to investigate its role in pathogenesis.MethodsFirst, an expression profile of circRNAs in the peripheral blood monocular cells of MDD patients and healthy peripherals were established based on high-throughput sequencing analysis. In addition, the top 10 differentially expressed circRNAs were quantified by quantitative real-time PCR to explore diagnostic biomarkers. To further investigate the function of biomarkers in the pathogenesis of MDD, bioinformatics analysis on downstream target genes of the biomarkers was carried out.ResultsThere is a mass of dysregulated circRNAs in PBMCs between female MDD patients and healthy controls. Among the top 10 differentially expressed circRNAs, hsa_circ_0126218 is more feasible as a diagnostic biomarker. The expression level of hsa_circ_0126218 displayed upregulation in patients with MDD and the area under the operating characteristic curve of hsa_circ_0126218 was 0.801 (95% CI 0.7226-0.8791, p < 0.0001). To explain the competing endogenous RNA role of hsa_circ_0126218 in the pathogenesis of female MDD, a hsa_circ_0126218-miRNA-mRNA network was established. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses stated that some of the enriched pathways downstream of hsa_circ_0126218 are closely related to MDD. Moreover, we established a protein-protein network to further screen out the hub genes (PIK3CA, PTEN, MAPK1, CDC42, Lyn, YES1, EPHB2, SMAD2, STAT1, and ILK). The function of hsa_circ_0126218 was refined by constructing a verified circRNA-predicted miRNA-hub gene subnetwork.Conclusionhsa_circ_0126218 can be considered as a new female MDD biomarker, and the pathogenesis of female MDD by the downstream regulation of hsa_circ_0126218 has been predicted. These findings may help further improve the early detection, effective diagnosis, convenient monitoring of complications, precise treatment, and timely recurrence prevention of depression.

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A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder.

Publications

A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder.

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