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Zhang Q.-L.,Xuzhou Medical College | Lu J.,GoPath Laboratories LLC | Sun X.-Y.,Prevention and Treatment Center for Psychological Diseases | Sun X.-Y.,Shanghai University | And 8 more authors.
European Journal of Psychiatry

Background and Objectives: Currently, there is a serious need to find practical biomarker(s) for Major Depressive Disorder (MDD) therapeutic target(s). This study aimed to investigate the association between microRNA (miRNA, miR) expression level in Peripheral Blood Mononuclear Cells (PBMCs) and symptomatology improvement in MDD patients before and after six-week antidepressant treatment. Methods: By using an Affymetrix array that covers 723 human miRNAs, 26 miRNAs were identified with significantly altered expression in PBMCs in MDD patients, of which 10 miRNAs were selected for quantitative real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) study. Twenty out of all the 81 MDD patients were selected for miRNA expression levels testing and symptomatology assessments before and after sixweek treatment. Results: Compared with the control group, the expression levels of miR-26b, miR- 4743, miR-4498, miR-4485 and miR-1972 of the MDD group were significantly higher (P < 0.05); the changes of expression levels of miR-4743, miR-4498, miR-4485 and miR- 1972 were positively related to retardation improvement (P < 0.05), and the change of expression level of miR-26b negatively to the improvement of day and night change (P < 0.05); regression analysis result demonstrated that the alteration of miR-4485 expression accounted for 28.8% of retardation improvement (P < 0.05). Conclusions: These five miRNAs (miR-4743, miR-4498, miR-4485, miR-1972 and miR-26b) may serve as biomarker for MDD diagnosis and therapeutic targets for MDD treatment. © 2014, University of Zaragoza. All rights reserved. Source

Sun X.-Y.,Prevention and Treatment Center for Psychological Diseases | Song H.-T.,Bengbu Medical College | Zhao L.,Guangji Hospital | Niu W.,102 Hospital of PLA | And 3 more authors.
Medical Journal of Chinese People's Liberation Army

Objective To observe the changes in microRNA (miRNA) expression levels in peripheral blood of schizophrenia patients before and after treatment with antipsychotics. Methods Sixty-one consecutive patients with schizophrenia (case group) and 62 normal controls (control group) hospitalized to the 102nd Hospital of PLA from July 2012 to May 2013 were involved in this study. The relative expression levels of 9 miRNAs (miR-181b, miR-195, miR-132, miR-212, miR-30e, miR-346, miR-34a, miR-432, miR-7) in the peripheral blood plasma of patients in two groups were determined by real-time fluorescence quantitative PCR. Twenty-five schizophrenia patients with total score of Positive and Negative Syndrome Scale (PANSS) >70 were selected to determine the miRNA expression levels before and 3 and 6 weeks after antipsychotics (including olanzapine, quetiapine, ziprasidone and risperidone) treatment, and the clinical symptoms and treatment effect in different stages of therapy were assessed by PANSS, Global Assessment Scale (GAS), and Clinical Global Impression scale (CGI). Results The expression levels of miR-181b, miR-30e, miR-346, miR-34a and miR-7 in case group were significantly higher than those in control group (P<0.05, P<0.01). In the 25 patients with PANSS >70, the expression level of miR-132 lowered 3 weeks after treatment (P<0.05), the expression levels of miR-132, miR-181b, miR-30e and miR-432 lowered 6 weeks after treatment (P<0.05, P<0.01) compared with those before treatment. After treatment for 6 weeks, all the expression levels of the 9 \miRNAs in 25 patients were similar to those in control group (P>0.05). The expression of miR-132, miR-195, miR-30e and miR-432 were significantly correlated with the PANSS total score and GAS score along with the treatment course (P<0.05). Conclusion The miR-181b, miR-132, miR-30e and miR-432 maybe used as biological markers for the prediction of the prognosis of patients with schizophrenia. © 2014, People's Military Medical Press. All rights reserved. Source

Fan H.-M.,Cadre Ward | Fan H.-M.,Shanghai University | Sun X.-Y.,Shanghai University | Sun X.-Y.,Prevention and Treatment Center for Psychological Diseases | And 8 more authors.
Journal of Molecular Neuroscience

Schizophrenia (SZ) is a debilitating psychotic disorder of unknown etiology, and the diagnosis is essentially based on clinical symptoms. So it is urgent to find an objective and feasible clinical diagnostic index for SZ. MicroRNA array was performed in peripheral blood mononuclear cells (PBMCs) obtained from young SZ patients and gender-, age-, and ethnicity-matched healthy controls. Then, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify the top 10 microRNAs (miRNAs) with the highest fold change values in 55 SZ patients and 28 healthy controls, and 9 miRNAs demonstrate significant differences in expression levels (P < 0.01). Receiver operating characteristic (ROC) curve analysis showed that the combining area under the ROC curve (AUC) of the nine miRNAs was 0.973 (95 % confidence interval (CI): 0.945–1.000). miRNA target gene prediction and functional annotation analysis showed that there were significant enrichments in several gene ontology (GO) biological process and Kyoto encyclopedia of genes and genomes (KEGG) pathways associated with nervous system and brain functions, suggesting that the differentially expressed miRNAs may be involved in mechanism of SZ. We conclude that altered expression of miRNAs in PMBCs might be involved in young SZ pathogenesis and may serve as noninvasive biomarker for SZ diagnosis. © 2015, Springer Science+Business Media New York. Source

Sun X.,Shanghai University | Sun X.,Prevention and Treatment Center for Psychological Diseases | Dai X.,Records Room | Yang T.,The General Hospital of Peoples Liberation Army | And 4 more authors.

The aim of this study was to investigate the effects of mental resilience on the changes of serum rennin, angiotensin, and cortisol level induced by sleep deprivation in servicemen. By random cluster sampling, a total of 160 servicemen, aged from 18 to 30, were selected to undergo 24-hour total sleep deprivation and administered the military personnel mental resilience scale after the deprivation procedure. The sleep deprivation procedure started at 8 a.m. on Day 8 and ended at 8 a.m. on Day 9 after 7 days of normal sleep for baseline preparation. Blood samples were drawn from the 160 participants at 8 a.m. respectively on Day 8 and Day 9 for hormonal measurements. All blood samples were analyzed using radioimmunoassay. As hypothesized, serum rennin, angiotensin II, and cortisol level of the participants after sleep deprivation were significantly higher than those before (P < 0.05). The changes of serum rennin and cortisol in the lower mental resilience subgroup were significantly greater (P < 0.05); problem-solving skill and willpower were the leading influence factors for the increases of serum rennin and cortisol respectively induced by sleep deprivation. We conclude that mental resilience plays a significant role in alleviating the changes of neurohormones level induced by sleep deprivation in servicemen. © 2014, Springer Science+Business Media New York. Source

Fan H.,General Hospital of Guangzhou Military Command | Fan H.,Prevention and Treatment Center for Psychological Diseases | Niu W.,No. 102 Hospital of Peoples Liberation Army | He M.,Prevention and Treatment Center for Psychological Diseases | And 4 more authors.
Chinese Journal of Medical Genetics

Objective To identify differentially expressed microRNAs(miRNA) in peripheral blood mononuclear cells(PBMCs) of anxiety patients and predict their target genes and function by bioinformatics analysis. Methods The miRNA expression profiles were determined using an Affymetrix array. To validate the results, real-time quantitative polymerase chain reaction(qRT-PCR) analysis in a larger cohort was employed. The targets of the differentially expressed miRNAs were predicted by Target Scan, miRBD, and DIANA-microT-CDS, and the results were analyzed by gene ontology (GO) and KEGG pathway analysis using FunNet. Results MicroRNA microarray chip analysis has identified 7 miRNAs were detected with significant changes in expression in PBMCs of anxiety patients. qRT-PCR analysis has confirmed that the expression levels of 5 miRNAs(has-miR-4484, has-miR-4505, has-miR-4674, has-miR-501-3p and has-miR-663) were up-regulated. Intersecting the genes by Target Scan, miRBD, and DIANA-microT-CDS has predicted 195 targets. GO analysis showed that biological processes regulated by the predicted target genes have included diverse terms. Some terms, e. g., nervous system development, nerve growth factor receptor signaling pathway, neuron migration, dendrite development, regulation of neuron projection development, midbrain development, regulation of excitatory postsynaptic membrane potential, gliogenesis, dendrite morphogenesis, etc. have direct relationship with the central nervous system and brain functions. Pathway analysis showed that a significant enrichment in several pathways related to neuronal brain functions such as glutamatergic synapse, axon guidance, calcium signaling pathway, MAPK signaling pathway, GnRH signaling pathway, Wnt signaling pathway, gap junction, long-term potentiation and VEGF signaling pathway, etc. Among the five microRNAs, has-miR-4484, has-miR-4505, has-miR-4674 and has-miR-501-3p may have more important regulatory functions. Conclusion Five miRNAs (has-miR-4484, has-miR-4505, has-miR-4674, has-miR ∼501-3p and has-miR-663) are up-regulated in PBMCs of anxiety patients and may be closely involved in the pathogenesis of anxiety disorder. Source

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