Search

Background. Acute type A aortic dissection (AAD) is a catastrophic disease with high mortality, but the pathogenesis has not been fully elucidated. This study is aimed at identifying hub genes and immune cells associated with the pathogenesis of AAD. Methods. The datasets were downloaded from Gene Expression Omnibus (GEO). Gene Set Enrichment Analysis (GSEA), gene set variation analysis (GSVA), and differential analysis were performed. The differentially expressed genes (DEGs) were intersected with specific genes collected from MSigDB. The gene function and pathway enrichment analysis were also performed on intersecting genes. The key modules were selected by weighted gene coexpression network analysis (WGCNA). Hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis and were verified in the metadataset. The immune cell infiltration was analyzed by CIBERSORT, and the relationship between hub genes and immune cells was performed by Pearson’s correlation analysis. The single-cell RNA sequencing (scRNA-seq) dataset was used to verify the differences in DNA damage and repair signaling pathways and hub genes in different cell types. Results. The results of GSEA and GSVA indicated that DNA damage and repair processes were activated in the occurrence of AAD. The gene function and pathway enrichment analysis on differentially expressed DNA damage- and repair-related genes showed that these genes were mainly involved in the regulation of the cell cycle process, cellular response to DNA damage stimulus, response to wounding, p53 signaling pathway, and cellular senescence. Three key modules were identified by WGCNA. Five genes were screened as hub genes, including CDK2, EIF4A1, GLRX, NNMT, and SLCO2A1. Naive B cells and Gamma delta T cells (γδ T cells) were decreased in AAD, but monocytes and M0 macrophages were increased. scRNA-seq analysis included that DNA damage and repair processes were activated in smooth muscle cells (SMCs), tissue stem cells, and monocytes in the aortic wall of patients with AAD. Conclusions. Our results suggested that DNA damage- and repair-related genes may be involved in the occurrence of AAD by regulating many biological processes. The hub genes and immune cells reported in this study also increase the understanding of AAD.

Aifang Zhong,1,2 Ning Ding,1,2 Yang Zhou,1,2 Guifang Yang,1,2 Zhenyu Peng,1,3 Hongliang Zhang,1,3 Xiangping Chai1,2 1Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Trauma center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Emergency Medicine and Difficult Disease Institute, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Xiangping ChaiCentral South University, 139 Renmin Middle Road, Changsha City, Hunan Province, People’s Republic of ChinaEmail chaixiangping@csu.edu.cnBackground: At present, the pathogenesis of intracranial aneurysms (IA) remains unclear, which significantly hinders the development of novel strategies for the clinical treatment. In this study, bioinformatics methods were used to identify the potential hub genes and pathways associated with the pathogenesis of IA.Methods: The gene expression datasets of patients with intracranial aneurysm were downloaded from the Gene Expression Database (GEO), and the different data sets were integrated by the robust rank aggregation (RRA) method to identify the differentially expressed genes between patients with intracranial aneurysm and the controls. The functional enrichment analyses of the significant differentially expressed genes (DEGs) were performed and the protein–protein interaction (PPI) network was constructed; thereafter, the hub genes were screened by cytoHubba plug-in of Cytoscape, and finally sequencing dataset GSE122897 was used to verify the hub genes.Results: The GSE15629, GSE75436, GSE26969, and GSE6551 expression profiles have been included in this study, including 34 intracranial aneurysm samples and 26 control samples. The four datasets obtained 136 significant DEGs (45 up-regulated, 91 down-regulated). Enrichment analysis showed that the extracellular matrix structural constituent and the ECM-receptor interaction were closely related to the occurrence of IA. It was finally determined that eight hub genes associated with the development of IA, including VCAN, COL1A1, COL11A1, COL5A1, COL5A2, POSTN, THBS2, and CDH2.Conclusion: The discovery of potential hub genes and pathways could enhance the understanding of the molecular mechanisms associated with the development of IA. These hub genes may be potential therapeutic targets for the management and new biomarker for the diagnosis of IA.Keywords: intracranial aneurysm, hub genes, robust rank aggregation

The characteristics of COVID-19 patients with autoimmune rheumatic diseases (AIRD) have rarely been reported. Patients with AIRD have suppressed immune defense function, which may increase their susceptibility to COVID-19. However, the immunosuppressive agents AIRD patients routinely used may be beneficial for protecting the cytokine storm caused by SARS-CoV-2. In this retrospective study, we included all confirmed cases in Huoshenshan Hospital from February 4 to April 9. Data were extracted from electronic medical records and were analyzed for clinical and laboratory features using SPSS (version 25.0). Of 3059 patients, 21 had the comorbidities with systematic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA), including 5 with SLE, 15 with RA, and 1 with Rhupus. The proportion was 57.1% for severe cases, 61.9% for either severe or critical cases, and 4.8% for critical cases. The main manifestations, ARDS and ICU admission rate, as well as the mortality and length of hospital stay of COVID-19 in AIRD patients were similar to COVID-19 patients in the general population. Our preliminary experience shows that patients with AIRD tend to have a higher risk of SARS-CoV-2 infection, and may be at risk for a severe but less likely critical disease course. Further investigation is needed to understand the immunological features of these diseases.

Deciphering the dynamic changes in antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. Here we analyze the laboratory findings of 1,850 patients to describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)-specific immunoglobulin M (IgM) and G (IgG) levels during SARS-CoV-2 infection and recovery. The generation of S-, RBD-, and N-specific IgG occurs one week later in patients with severe/critical COVID-19 compared to patients with mild/moderate disease, while S- and RBD-specific IgG levels are 1.5-fold higher in severe/critical patients during hospitalization. The RBD-specific IgG levels are 4-fold higher in older patients than in younger patients during hospitalization. In addition, the S- and RBD-specific IgG levels are 2-fold higher in the recovered patients who are SARS-CoV-2 RNA negative than those who are RNA positive. Lower S-, RBD-, and N-specific IgG levels are associated with a lower lymphocyte percentage, higher neutrophil percentage, and a longer duration of viral shedding. Patients with low antibody levels on discharge might thereby have a high chance of being tested positive for SARS-CoV-2 RNA after recovery. Our study provides important information for COVID-19 diagnosis, treatment, and vaccine development., Understanding antibody responses to Sars-CoV-2 proteins over time is complicated by many variables. Here the authors survey IgM and IgG antibodies against S protein, RBD and nucleoprotein in a large cohort of infected and recovering severe vs. moderate COVID-19 patients, comparing against clinical parameters and immunological readouts.

In the current issue of Blood, Xia et al evaluate the use of convalescent plasma for the treatment of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19).1,2 SARS-CoV-2 has spurred a global crisis. To date, there are limited treatment options for COVID-19 and no proven prophylactic therapies for those who have been exposed to SARS-CoV-2.

How SARS-CoV-2 causes disturbances of the lung microenvironment and systemic immune response remains a mystery. Here, we first analyze detailedly paired single-cell transcriptome data of the lungs, blood and bone marrow of two patients who died of COVID-19. Second, our results demonstrate that SARS-CoV-2 infection significantly increases the cellular communication frequency between AT1/AT2 cells and highly inflammatory myeloid cells, and induces the pulmonary inflammation microenvironment, and drives the disorder of fibroblasts, club and ciliated cells, thereby causing the increase of pulmonary fibrosis and mucus accumulation. Third, our works reveal that the increase of the lung T cell infiltration is mainly recruited by myeloid cells through certain ligands/receptors (ANXA1/FPR1, C5AR1/RPS19 and CCL5/CCR1), rather than AT1/AT2. Fourth, we find that some ligands and receptors such as ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1, are significantly activated and shared among patients’ lungs, blood and bone marrow, implying that dysregulated ligands and receptors may cause the migration, redistribution and the inflammatory storm of immune cells in different tissues. Overall, our study reveals a latent mechanism by which the disorders of ligands and receptors caused by SARS-CoV-2 infection drive cell communication alteration, the pulmonary inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

Objectives: Earlier researches suggested patients should be routinely screened for bacteria and fungi infection after COVID-19 being confirmed. Here, we enrolled 236 patients with COVID-19 to analyze the clinical characteristics, fungal strains, mortality, and laboratory data of different groups. Design: Single center retrospective study Patients: A total of 236 COVID-19 patients from Huoshenshan Hospital were included in this study, consisting of 14(6%) died cases, 222(94%) discharged cases . Results: The result revealed that 5 mortality in positive group were all related to aspergillus infection while candida infection rarely caused death. Aspergillus was most common in non-survivors while candida was most common in survivors. In terms of interleukin-6 (IL6), viral loads, nucleic acid clearance time, etc, fungal serologically positive group had a higher level than negative group. Conclusions: Non-survivors of Covid-19 with fungal infection were almost associated with aspergillus infection. Aspergillus infection, instead of candida infection might be fatal for critical ill patients with COVID-19. There is great significance to carry out routine screening for fungal infection especially for critical patients to enable early treatment to be implemented. Keywords: coronavirus disease 2019 (COVID-19); fungal infection; aspergillus; mortality

Deciphering the dynamic changes of antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. By comprehensively analyzing the laboratory findings of 1,850 patients, we describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels during SARS-CoV-2 infection and recovery. Our results indicate that the S-, RBD-, and N- specific IgG generation of severe/critical COVID-19 patients is one week later than mild/moderate cases, while the levels of these antibodies are 1.5-fold higher in severe/critical patients during hospitalization (P

Objectives: Earlier researches suggested patients should be routinely screened for bacteria and fungi infection after COVID-19 being confirmed. Here, we enrolled 236 patients with COVID-19 to analyze the clinical characteristics, fungal strains, mortality, and laboratory data of different groups. Design: Single center retrospective study Patients: A total of 236 COVID-19 patients from Huoshenshan Hospital were included in this study, consisting of 14(6%) died cases, 222(94%) discharged cases. Results: The result revealed that 5 mortality in positive group were all related to aspergillus infection while candida infection rarely caused death. Aspergillus was most common in non-survivors while candida was most common in survivors. In terms of interleukin-6 (IL6), viral loads, nucleic acid clearance time, etc, fungal serologically positive group had a higher level than negative group. Conclusions: Non-survivors of Covid-19 with fungal infection were almost associated with aspergillus infection. Aspergillus infection, instead of candida infection might be fatal for critical ill patients with COVID-19. There is great significance to carry out routine screening for fungal infection especially for critical patients to enable early treatment to be implemented. Funding Statement: This study was financially supported by grants Key Foundation of Wuhan Huoshenshan Hospital (2020[18]), Key Research& Development Program of Jiangsu Province (BE2018713), Medical Innovation Project of Logistics Service (18JS005). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Medical Ethical Committee of Wuhan Huoshenshan Hospital (No. HSSLL011). Written informed consent was obtained from each patient.

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.

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.

BACKGROUND The criteria for diagnosing depression are based on behavioral observation and self-reporting of symptoms by the patients or guardians without any biological validation of the disease. This study aimed to identify long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) as robust and predictive biomarkers for diagnosis and therapy response in major depressive disorder (MDD). MATERIAL AND METHODS We used human lncRNA 3.0 microarray profiling (which covers 30,586 human lncRNAs), using PBMCs from five MDD patients and five controls. Differentially expressed lncRNAs in the PBMCs of MDD patients were identified, of which 10 candidate lncRNAs were selected for real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in a larger cohort of 138 MDD patients and 63 healthy controls. Then among the 138 MDD patients who received standard antidepressant treatment, 30 were randomly selected for lncRNAs expression retesting and symptomatology assessments after three-weeks and six-weeks of antidepressant treatment. RESULTS Six lncRNAs (TCONS_00019174, ENST00000566208, NONHSAG045500, ENST00000517573, NONHSAT034045, and NONHSAT142707) were significantly downregulated in MDD patients compared to control patients, and the area under the receiver operator curve (ROC) of these six lncRNAs cases, combined, was 0.719 (95% confidence interval (CI): 0.617-0.821). There was no difference in the expression of these six lncRNAs based on gender (p>0.05) or age (p>0.05). CONCLUSIONS These results suggest that the combined expression of six lncRNAs in PBMCs may serve as a potential biomarker for diagnosis and therapy response of MDD in the clinical setting.

BACKGROUND Dysfunction of long non-coding RNAs (lncRNAs) has been demonstrated to be involved in psychiatric diseases. However, the expression patterns and functions of the regulatory lncRNAs in schizophrenia (SZ) patients have rarely been systematically reported. MATERIAL AND METHODS The lncRNAs in peripheral blood mononuclear cells (PBMCs) were screened and compared between the SZ patients and demographically-matched healthy controls using microarray analysis, and then were validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) method. Three verified significantly dysregulated lncRNAs of PBMCs were selected and then measured in SZ patients before and after the antipsychotic treatment. SZ symptomatology improvement was measured by Positive And Negative Syndrome Scale (PANSS) scores. RESULTS One hundred and twenty-five lncRNAs were significantly differentially expressed in SZ patients compared with healthy controls, of which 62 were up-regulated and 63 were down-regulated. Concurrent with the significant decrease of the PANSS scores of patients after the treatment, the PBMC levels of lncRNA NONHSAT089447 and NONHSAT041499 were strikingly decreased (P

MicroRNAs (miRNA, miR) have been implicated as promising blood-based biomarkers for schizophrenia patients. This study aimed to clinically validate miRNA as potential schizophrenia biomarkers. Plasma levels of 10 miRNAs were analyzed using qPCR in a cohort of 61 schizophrenia patients and 62 normal controls, as well as 25 patients particularly selected for a six-week antipsychotic treatment course. Positive And Negative Syndrome Scale (PANSS), Global Assessment Scale (GAS) and Clinical Global Impression (CGI) were administered to assess the clinical symptoms. The results demonstrated that a panel of miRNAs consisting of miR-30e, miR-181b, miR-34a, miR-346 and miR-7 had significantly increased expression levels with significant combined diagnostic value (AUC:0.713; sensitivity:35.5%; specificity:90.2%). In response to pharmacological treatment, expression levels of miR-132, miR-181b, miR-432 and miR-30e were significantly decreased. In addition, the improvement of clinical symptomatology was significantly correlated with the changes of miR-132, miR-181b, miR-212 and miR-30e expression levels. Furthermore, the decreases of plasma levels of miR-132 and miR-432 were significantly greater in high-effect subgroup than those in low-effect subgroup after six-week treatment course. We conclude that miR-30e, miR-181b, miR-34a, miR-346 and miR-7 combined as a panel are potentially useful non-invasive biomarkers for schizophrenia diagnosis. Markers miR-132, miR-181b, miR-30e and miR-432 are potential indicators for symptomatology improvements, treatment responses and prognosis for schizophrenia patients.

Introduction This study aims to investigate the effects of childhood maltreatment on neurological soft signs (NSS) associated with certain brain area in depressive patients. Methods One hundred three depressive patients were enrolled into this study, and evaluated by Childhood Trauma Questionnaire (CTQ), brain area-related neurological examination scale, 24-item Hamilton Rating scale (HAMD24), the scale for suicidal ideation (SSI) and Beck Hopelessness Scale (BHS). Results Patients undergoing childhood maltreatment exhibited higher frontal area-related NSS scores than patients without childhood maltreatment experience. Patients experiencing childhood emotional or physical neglect displayed more frontal area-related NSS compared to their respective non-maltreatment group. Moreover, physical neglect maltreatment caused more temporal area-related NSS. Patients suffering from childhood sexual abuse had more frontal, temporal and occipital area-related NSS than patients lacking experience of childhood sexual abuse. Further correlation analysis revealed that the total score of maltreatment positively correlated with frontal and temporal area-related NSS score. There was a positive correlation between emotional abuse, emotional neglect or physical abuse and frontal area-related NSS. Physical neglect and sexual abuse were positively associated with the temporal area-related NSS score. HAMD24 score was positively correlated with all brain area-related NSS score; The SSI score correlated with three area (excluded occipital area)-related NSS score. The BHS score only positively correlated with frontal area score of NSS. Finally, no significant association was found between suicidal frequencies and brain area-related NSS score. Discussion Childhood maltreatment adversely affects the brain of depressive patients; the different maltreatment may impair different brain areas, especially frontal and temporal areas.

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.

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.

OBJECTIVE To identify differentially expressed microRNA (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.

This study investigated the correlation between the level of microRNA expression in peripheral blood mononuclear cells (PBMCs) and symptomatology in patients with generalized anxiety disorder (GAD). MicroRNA array was performed in peripheral blood mononuclear cells (PBMCs) obtained from GAD patients with gender, age, ethnicity-matched healthy controls. Then real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify the top 7 miRNAs with the highest fold-change values in 76 GAD patients and 39 healthy controls. It demonstrated that 5 miRNAs showed significantly differences in expression levels (P

Schizophrenia is a severe and debilitating psychiatric disorder of unknown etiology, and its diagnosis is essentially based on clinical symptoms. Despite growing evidence on the relation of altered expression of miRNAs and schizophrenia, most patients with schizophrenia usually had an extensive antipsychotic treatment history before miRNA expression profile analysis, and the pharmacological effects on miRNA expression are largely unknown. To overcome these impediments, miRNA microarray analysis was performed in peripheral blood mononuclear cells (PBMCs) obtained from patients with schizophrenia who were not on antipsychotic medication and healthy controls. Then, using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we verified the top 10 miRNAs with the highest fold-change values from microarray analysis in 82 patients with schizophrenia and 43 healthy controls, and nine miRNAs demonstrated significant differences in expression levels. Finally, we compared these nine miRNA profiles before and after antipsychotic treatment. Our results revealed that serum miR-21 expression decreased strikingly in patients after antipsychotic treatment. The change of miR-21 expression was negatively correlated with improvement of positive, general psychopathology, and aggressiveness symptoms. This study preliminarily analyzed the possible changes in circulating miRNAs expression in response to antipsychotic medication for schizophrenia, and the molecular mechanisms of this needs to be further explored.

Background WHO stated that nearly one million people commit suicide every year worldly, and 40% of the suicide completer suffered from depression. The primary aim of this study was to explore the association between long noncoding RNAs (lncRNAs) expression in peripheral blood mononuclear cells (PBMCs) and suicide risk of patients with major depressive disorder (MDD). Methods Using Human LncRNA 3.0 microarray profiling which includes 30,586 human lncRNAs and RT-PCR, six down-regulated lncRNAs were identified differentially expressed in MDD patients. According to suicidal ideation and suicidal attempt, the suicide risk of MDD patients was classified into suicidal ideation versus no suicidal ideation groups, and past attempt versus no past attempt groups, respectively. The expression of six lncRNAs in MDD patients and controls were examined by RT-PCR. Results The expression of six lncRNAs had significant differences between no suicidal ideation, suicidal ideation, and controls; corresponding lncRNAs associated with suicidal attempt had remarkable differences between no past attempt, past attempt, and controls. Additionally, only the expression of lncRNAs in suicidal ideation group and past attempt group markedly declined compared with controls. Conclusions This study indicated that the expression of six down-regulated lncRNAs had a negative association with suicide risk in MDD patients, and the expression of lncRNAs in PBMCs could have the potential to help clinician judge the suicide risk of MDD patients to provide timely treatment and prevent suicide.

Background: About half of patients with major depressive disorder (MDD) have clinically meaningful levels of anxiety. Greater severity of depressive illness and functional impairment has been reported in patients with high levels of anxiety accompanying depression. The pathogenesis for the comorbidity was still unsure. Aim: This study aimed to determine whether there would be molecular link for overlapped pathogenesis between MDD and anxiety disorder. Materials and Methods: Using long noncoding RNA (lncRNA) microarray profiling and reverse transcription polymerase chain reaction, six downregulated lncRNAs and three upregulated lncRNAs had been identified to be the potential biomarkers for MDD and generalized anxiety disorder (GAD), respectively. Then, the lncRNAs were cross-checked in forty MDD patients, forty GAD patients, and forty normal controls. Results: Compared with normal controls, six downregulated MDD lncRNAs also had a significantly lower expression in GAD (P < 0.01), and there was no significant difference between GAD and MDD (P > 0.05). In addition, three upregulated GAD lncRNAs had no different expression in MDD (P > 0.05), but there was remarkable difference between MDD and GAD (P < 0.01). Conclusions: These results indicated that lncRNAs in peripheral blood mononuclear cells could be potential molecular link between MDD and GAD, which added new evidence to the overlapped pathogenesis and suggested that anxious depression could be a valid diagnostic subtype of MDD.

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.

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.

This study aims to investigate the effects of childhood maltreatment on neurological soft signs (NSS) associated with certain brain area in depressive patients.One hundred three depressive patients were enrolled into this study, and evaluated by Childhood Trauma Questionnaire (CTQ), brain area-related neurological examination scale, 24-item Hamilton Rating scale (HAMD24), the scale for suicidal ideation (SSI) and Beck Hopelessness Scale (BHS).Patients undergoing childhood maltreatment exhibited higher frontal area-related NSS scores than patients without childhood maltreatment experience. Patients experiencing childhood emotional or physical neglect displayed more frontal area-related NSS compared to their respective non-maltreatment group. Moreover, physical neglect maltreatment caused more temporal area-related NSS. Patients suffering from childhood sexual abuse had more frontal, temporal and occipital area-related NSS than patients lacking experience of childhood sexual abuse. Further correlation analysis revealed that the total score of maltreatment positively correlated with frontal and temporal area-related NSS score. There was a positive correlation between emotional abuse, emotional neglect or physical abuse and frontal area-related NSS. Physical neglect and sexual abuse were positively associated with the temporal area-related NSS score. HAMD24 score was positively correlated with all brain area-related NSS score; The SSI score correlated with three area (excluded occipital area)-related NSS score. The BHS score only positively correlated with frontal area score of NSS. Finally, no significant association was found between suicidal frequencies and brain area-related NSS score.Childhood maltreatment adversely affects the brain of depressive patients; the different maltreatment may impair different brain areas, especially frontal and temporal areas.

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.