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Cui X.,Nanjing Medical University | Niu W.,Chinese People's Liberation Army | Kong L.,Chinese People's Liberation Army | He M.,Chinese People's Liberation Army | And 8 more authors.
Biomarkers in Medicine | Year: 2017

Aim: Depression and anxiety are common symptoms for schizophrenia (SZ) in the early onset. This study aimed to determine whether long noncoding RNAs (lncRNAs) can be indicators for diagnosing SZ in nonpsychiatric hospitals. Materials & methods: Three upregulated SZ lncRNAs, six downregulated major depressive disorder (MDD) lncRNAs and three upregulated generalized anxiety disorder (GAD) lncRNAs were cross-validated in 45 SZ patients, 48 MDD patients, 52 GAD patients and 40 controls by reverse transcription-PCR. Results: Three SZ lncRNAs were significantly downregulated in GAD patients. The expression of the six MDD lncRNAs showed an opposite trend in SZ patients, and the three GAD lncRNAs also showed significant differences between SZ and GAD patients. Conclusion: The three upregulated SZ lncRNAs are not entirely replicated in MDD and GAD patients and could be potential indicators for distinguishing SZ from MDD and GAD in nonpsychiatric hospital. © 2017 Future Medicine Ltd.


Kong L.,Prevention And Treatment Center For Psychological Diseasesno 102 Hospital Of The Chinese Peoples Liberation Armychangzhoupeoples Republic Of China | He M.,Prevention And Treatment Center For Psychological Diseasesno 102 Hospital Of The Chinese Peoples Liberation Armychangzhoupeoples Republic Of China | Jiang K.,Prevention And Treatment Center For Psychological Diseasesno 102 Hospital Of The Chinese Peoples Liberation Armychangzhoupeoples Republic Of China | Zhong A.,Clinical Laboratoryno 102 Hospital Of The Chinese Peoples Liberation Armychangzhoupeoples Republic Of China | And 3 more authors.
American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | Year: 2017

Depression and anxiety are apparent symptoms in the early onset or acute phase of schizophrenia (SZ), which complicate timely diagnosis and treatment. It is imperative to seek an indicator to distinguish schizophrenia from depressive and anxiety disorders. Using lncRNA microarray profiling and RT-PCR, three up-regulated lncRNAs in SZ, six down-regulated lncRNAs in major depressive disorder (MDD), and three up-regulated lncRNAs in generalized anxiety disorder (GAD) had been identified as potential biomarkers. All the lncRNAs were, then, cross-validated in 40 SZ patients, 40 MDD patients, 40 GAD patients, and 40 normal controls. Compared with controls, three up-regulated SZ lncRNAs had a significantly down-regulated expression in GAD, and no remarkable differences existed between MDD and the controls. Additionally, the six down-regulated MDD lncRNAs were expressed in an opposite fashion in SZ, and the expression of the three up-regulated GAD lncRNAs were significantly different between SZ and GAD. These results indicate that the expression patterns of the three up-regulated SZ lncRNAs could not be completely replicated in MDD and GAD, and vice versa. Thus, these three SZ lncRNAs seem to be established as potential indicators for diagnosis of schizophrenia and distinguishing it from MDD and GAD. © 2017 Wiley Periodicals, Inc.


Fan H.-M.,Chengdu Military General Hospital | Fan H.-M.,Shanghai University | Sun X.-Y.,Shanghai University | Sun X.-Y.,No102 Hospital Of Chinese Peoples Liberation Army | And 8 more authors.
Journal of Molecular Neuroscience | Year: 2015

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.


Fan H.-M.,Shanghai University | Sun X.-Y.,Shanghai University | Sun X.-Y.,Chinese People's Liberation Army | Guo W.,Chinese People's Liberation Army | And 9 more authors.
Journal of Psychiatric Research | Year: 2014

Currently, diagnosis and treatment of major depressive disorder (MDD) are based on the patients' description of symptoms, mental status examinations, and clinical behavioral observations, which increases the chance of misdiagnosis. There is a serious need to find a practical biomarker for the proper diagnosis of MDD. This study aimed to explore the possibility of microRNA (miRNA) in peripheral blood mononuclear cells (PBMCs) as specific blood-based biomarker for MDD patients. By using an Affymetrix array that covers 723 human miRNAs, we identified 26 miRNAs with significant changes in expression in PBMCs of MDD patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in a larger cohort of 81 MDD patients and 46 healthy controls confirmed that the expression levels of 5 miRNAs (miRNA-26b, miRNA-1972, miRNA-4485, miRNA-4498, and miRNA-4743) were up-regulated. By receiver operating characteristic (ROC) curve analysis, the combining area under the ROC curve (AUC) of these five miRNAs was 0.636 [95% confidence interval (CI): 0.58-0.90]. MiRNA target gene prediction and functional annotation analysis showed that there was a significant enrichment in several pathways associated with nervous system and brain functions, supporting the hypothesis that differentially-regulated miRNAs may be involved in mechanism underlying development of MDD. We conclude that altered expression of miRNAs in PMBCs might be involved in multiple stages of MDD pathogenesis, and thus might be able to serve as specific biomarker for diagnosis of MDD. © 2014 Elsevier Ltd. All rights reserved.


Song H.-T.,Bengbu Medical College | Sun X.-Y.,Shanghai University | Sun X.-Y.,Chinese People's Liberation Army | Zhang L.,First Center for Mental Health of Civil Affairs Bureau | And 10 more authors.
Journal of Psychiatric Research | Year: 2014

Despite the growing evidences on the relation of altered expression of miRNAs and schizophrenia, most schizophrenia subjects have an extensive antipsychotic treatment history and the pharmacological effects on miRNA expression are largely unknown. This study aimed to investigate the change of plasma microRNA-181b level and improvement of symptomatology before and after six-week antipsychotic treatment in schizophrenia patients, and explore their association. A total of 20 schizophrenia patients absent of antipsychotics and 20 age-and gender-matched normal controls were enrolled, and tested for 9 schizophrenia-associated microRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) expression levels in plasma using quantitative RT-PCR and for symptomatology improvement using Positive And Negative Syndrome Scale (PANSS) before and after treatment (olanzapine, quetiapine, ziprasidone and risperidone) for the patients only. Compared with the normal control group, the expression levels of miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 of the patients group were significantly higher (p < 0.05). Compared with those before treatment in the patient group, the symptomatology scores were significantly lower (p < 0.001), and the expression level of microRNA-181b was significantly down-regulated after treatment (p < 0.05). The change of miRNA-181b expression was positively correlated with the improvement of negative symptoms and lack of response symptoms (r = 0.502 and 0.557, P < 0.05, accounting for 20.2% and 26.4% respectively), and their therapeutic effects with OR being 11.283 and 5.119 respectively. We conclude that miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 are probably involved in pathogenesis of SZ, and the significant down-regulation of miRNA-181b expression predicts improvement of negative symptoms to treatment, and thus can serve as a potential plasmamolecular marker for antipsychotic responses. © 2014 Elsevier Ltd.


Sun X.-Y.,Shanghai University | Sun X.-Y.,Chinese People's Liberation Army | Lu J.,GoPath Laboratories LLC | Lu J.,GoPath Diagnostics Laboratories Ltd | And 12 more authors.
Journal of Clinical Neuroscience | Year: 2015

Findings from multiple studies on microRNA (miRNA) expression profiling in schizophrenia patients have produced conflicting results. In order to investigate miRNA as specific biomarkers in the peripheral plasma and peripheral blood mononuclear cells (PBMC) of schizophrenia patients, expression levels of the nine most frequently reported schizophrenia-associated miRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) were examined in the peripheral plasma and PBMC in 25 schizophrenia patients and 13 healthy controls using quantitative real-time reverse transcription polymerase chain reaction. We observed significantly increased expressions of miR-132, miR-195, miR-30e and miR-7 in plasma samples (p < 0.05 to p < 0.001), and miR-212, miR-34a and miR-30e in PBMC samples (p < 0.05 to p < 0.01). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) of miR-30e in plasma was 0.767 (95% confidence interval [CI] 0.608-0.926) with sensitivity and specificity of 90.90% and 60.00% respectively, and the AUC of miR-30e in PBMC was 0.756 (95% CI 0.584-0.929) with sensitivity and specificity of 81.80% and 68.00%, respectively. Logistic regression analysis demonstrated that miR-30e in plasma was more sensitive to differentiate schizophrenia patients from normal controls than miR-30e in PBMC. Our findings indicate that miRNA expression is more significant in plasma than in PBMC, and suggest that miR-30e in plasma may be a more sensitive biomarker for schizophrenia diagnosis, although its aberrant expression can be detected in both plasma and PBMC. © 2014 Elsevier Ltd.


Song H.-T.,Jiangsu University | Guo W.,2102 Hospital of PLA | Sun X.-Y.,Shanghai University | Zhang L.,Jiangsu University | And 6 more authors.
Medical Journal of Chinese People's Liberation Army | Year: 2014

Objective To explore the correlation between the microRNA expression in plasma and psychiatric symptoms in schizophrenia patients. Methods A total of 53 consecutive schizophrenia patients who had not received antipsychotic treatment from July 2012 to May 2013 were enrolled in the present study. The expressions of 9 schizophrenia-associated microRNAs (miR- 30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) in plasma were determined by real-time fluorescence quantitative PCR, with the psychiatric symptoms evaluated by Positive and Negative Symptoms Scale (PANSS), and the results were analyzed statistically. Results The expression level of miRNA-34a was significantly negatively correlated with the active symptoms and aggressive symptoms (r=-0.345, r=-0.284, P<0.05), and the expression level of miRNA-346 was significantly negatively correlated with the general psychopathologic symptoms (r=-0.282, P<0.05). The scores of activity and aggressiveness in the higher expression subgroup of miRNA-34a were significantly lower than those in lower expression subgroup (P<0.05). The score of disturbance of thought in the higher expression subgroup of miRNA-346 was significantly lower than that in lower expression subgroup (P<0.05). When miRNA-34a was entered into the two regression equations with the activity and aggressiveness as the independent variables respectively, it explained 10.2% of the variance of activity and 6.3% of the variance of aggressiveness.


PubMed | GoPath Diagnostics Laboratories Ltd, First Center for Mental Health of Civil Affairs Bureau, GoPath Laboratories LLC, Suzhou Psychiatric Hospital and 3 more.
Type: Journal Article | Journal: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia | Year: 2015

Findings from multiple studies on microRNA (miRNA) expression profiling in schizophrenia patients have produced conflicting results. In order to investigate miRNA as specific biomarkers in the peripheral plasma and peripheral blood mononuclear cells (PBMC) of schizophrenia patients, expression levels of the nine most frequently reported schizophrenia-associated miRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) were examined in the peripheral plasma and PBMC in 25 schizophrenia patients and 13 healthy controls using quantitative real-time reverse transcription polymerase chain reaction. We observed significantly increased expressions of miR-132, miR-195, miR-30e and miR-7 in plasma samples (p<0.05 to p<0.001), and miR-212, miR-34a and miR-30e in PBMC samples (p<0.05 to p<0.01). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) of miR-30e in plasma was 0.767 (95% confidence interval [CI] 0.608-0.926) with sensitivity and specificity of 90.90% and 60.00% respectively, and the AUC of miR-30e in PBMC was 0.756 (95% CI 0.584-0.929) with sensitivity and specificity of 81.80% and 68.00%, respectively. Logistic regression analysis demonstrated that miR-30e in plasma was more sensitive to differentiate schizophrenia patients from normal controls than miR-30e in PBMC. Our findings indicate that miRNA expression is more significant in plasma than in PBMC, and suggest that miR-30e in plasma may be a more sensitive biomarker for schizophrenia diagnosis, although its aberrant expression can be detected in both plasma and PBMC.


Cui X.,Nanjing Medical University | Niu W.,Chinese People's Liberation Army | Kong L.,Chinese People's Liberation Army | He M.,Chinese People's Liberation Army | And 7 more authors.
Biomarkers in Medicine | Year: 2016

Aim: This study aimed to determine whether circular RNA (circRNA) molecules in peripheral blood mononuclear cells (PBMCs) could be used as novel non-invasive biomarkers for major depressive disorder (MDD). Materials & methods: Differentially expressed circRNAs were screened using an Arraystar Human CircRNA Array (which includes 13,617 human circRNAs) and qRT-PCR. Thirty MDD patients were randomly selected to retest the circRNA levels after 4-week and 8-week antidepressant regimens. Results: Four differentially expressed circRNAs were identified between MDD patients and controls, and only down-regulated hsa-circRNA-103636 was significantly altered after the 8-week treatment in MDD patients. Conclusion: These results suggest that altered expression of hsa-circRNA-103636 in PBMCs is a potential novel biomarker for the diagnosis and treatment of MDD. © 2016 Future Medicine Ltd.


Sun X.-Y.,102 Hospital of PLA | Song H.-T.,Bengbu Medical College | Zhao L.,Guangji Hospital | Zhong A.-F.,102 Hospital of PLA | And 4 more authors.
Medical Journal of Chinese People's Liberation Army | Year: 2014

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.

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