Altered expression of mRNA profiles in blood of early-onset schizophrenia.
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ABSTRACT:
SUBMITTER: Xu Y
PROVIDER: S-EPMC4702094 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Schizophrenia (SZ) is a severe chronic psychiatric disorder with wide prevalence and high morbidity. We know little about SZ's etiology and pathophysiology at present. The study of gene expression profile is useful for us to identify potential biomarkers at molecular level and explain possible pathogenesis of SZ. Therefore we recently compared gene expression profiles in PMBCs from EOS cases and healthy controls using microarrays. Here we will describe in detail the contents and quality control of the microarray experiment. The raw microarray data are accessible through GEO series accession number GSE54913.
| S-EPMC4583616 | biostudies-literature
Project description:Existence of aging associated transcriptional differences in the schizophrenia brain was investigated in RNA sequencing data from 610 postmortem Dorso-Lateral Pre-Frontal Cortex (DLPFC) samples in the CommondMind Consortium (CMC) and the psychENCODE cohorts. This analysis discovered that the trajectory of gene expression changes that occur during brain aging differed between schizophrenia cases and unaffected controls. Mainly, the identified gene expression differences between the diagnosis groups shrank in magnitude following 60 years of age. A differential expression analysis restricted to the 40 to 60 year age group identified 556 statistically significant loci that replicated and had highly consistent gene expression fold changes in the two cohorts. An interaction between age and diagnosis in the wider psychENCODE cohort was also detected. Gene set enrichment analysis discovered disruptions in mitochondria, RNA splicing and phosphoprotein gene pathways. The identified differentially expressed genes in the two cohorts were also significantly enriched in genomic regions associated with schizophrenia although no enrichment was observed for differentially expressed genes identified in the 40 to 60 year age group. This work implicates disruptions to the normal brain aging processes in the pathology of schizophrenia and demonstrates the need for age stratification in schizophrenia postmortem brain gene expression studies.
| S-EPMC6459977 | biostudies-literature
Project description:We investigated associations of early pregnancy maternal vitamin D concentrations with differential gene expression and post-transcription regulation.Plasma 25-hydroxyvitamin D (25[OH]D) was measured among participants of a nested case-control study. Participants with low (<25.5 ng/ml) and high (?31.7 ng/ml) 25[OH]D were identified among controls. Peripheral blood messenger RNA (mRNA) (N?=?21) and microRNA (miRNA) (N?=?13) expression studies were conducted among participants with low and high 25[OH]D concentrations. Differential expression between low/high groups were evaluated using Student's t-test, fold change, and SAM comparisons. We further investigated functions and functional relationships of differentially expressed mRNAs and targets of differentially expressed miRNAs.Three hundred and five genes (299 upregulated and 6 downregulated) and 11 miRNAs (10 downregulated and 1 upregulated) were differentially expressed among participants with low 25[OH]D compared with those who had high 25[OH]D. Genes that participate in a wide range of cellular functions, including organ and system development (e.g. angiogenesis), inflammation and metabolic processes (e.g. carbohydrate/lipid metabolism), as well as miRNAs that target these genes were differentially expressed among women with low 25[OH]D compared with those with high 25[OH]D.Early pregnancy plasma 25[OH]D concentrations are associated with maternal peripheral blood gene expression and post-transcription regulation.
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Project description:A recent view on schizophrenia phenomenology underlines the impaired relations between the mind and the body. An aberrant feeling of ipseity may be the real source of suffering of the patients from psychosis and impacts general symptomatology. The disturbed connection between thinking processes and environmental stimuli may lead to language disembodiment. In the study, we aimed to experimentally test the presence of disembodied language and investigate its association with symptoms of psychosis in adolescents diagnosed with early-onset schizophrenia spectrum disorders. Assessment of language embodiment was conducted using the Zabór Verbal Task (ZVT) with concurrent linguistic and clinical assessment using the Thought, Language, and Communication Scale (TLCS) and Positive and Negative Symptoms Scale (PANSS). The study group of patients (n = 31) aged 11-18 years, with the diagnosis of schizophrenia spectrum according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and the International Classification of Diseases (ICD-10) criteria, was compared with a sex- and age-matched healthy control sample (n = 31). Patients with psychosis made more errors in ZVT than healthy controls (p = 0.01) and this parameter did not improve after 6-8 weeks of standard treatment (p = 0.55). A higher number of errors in ZVT were associated with the presence of auditory hallucinations (odds ratio [OR] 1.14; 95% CI 1.02-1.26). ZVT errors coincided with perception disorders, alternatively to the TLCS scores where we observed association with abnormal beliefs. The results of these preliminary studies indicate the value of the phenomenological approach in the diagnosis of schizophrenia spectrum and suggest a potential involvement of language disembodiment in symptomatology.
| S-EPMC9294146 | biostudies-literature
Project description:BackgroundWhole-genome expression studies in the peripheral tissues of patients affected by schizophrenia (SCZ) can provide new insight into the molecular basis of the disorder and innovative biomarkers that may be of great utility in clinical practice. Recent evidence suggests that skin fibroblasts could represent a non-neural peripheral model useful for investigating molecular alterations in psychiatric disorders.MethodsA microarray expression study was conducted comparing skin fibroblast transcriptomic profiles from 20 SCZ patients and 20 controls. All genes strongly differentially expressed were validated by real-time quantitative PCR (RT-qPCR) in fibroblasts and analyzed in a sample of peripheral blood cell (PBC) RNA from patients (n = 25) and controls (n = 22). To evaluate the specificity for SCZ, alterations in gene expression were tested in additional samples of fibroblasts and PBCs RNA from Major Depressive Disorder (MDD) (n = 16; n = 21, respectively) and Bipolar Disorder (BD) patients (n = 15; n = 20, respectively).ResultsSix genes (JUN, HIST2H2BE, FOSB, FOS, EGR1, TCF4) were significantly upregulated in SCZ compared to control fibroblasts. In blood, an increase in expression levels was confirmed only for EGR1, whereas JUN was downregulated; no significant differences were observed for the other genes. EGR1 upregulation was specific for SCZ compared to MDD and BD.ConclusionsOur study reports the upregulation of JUN, HIST2H2BE, FOSB, FOS, EGR1 and TCF4 in the fibroblasts of SCZ patients. A significant alteration in EGR1 expression is also present in SCZ PBCs compared to controls and to MDD and BD patients, suggesting that this gene could be a specific biomarker helpful in the differential diagnosis of major psychoses.
| S-EPMC4319917 | biostudies-literature
Project description:BackgroundSchizophrenia (SCZ) is a heritable, refractory, and devastating psychiatric disorder. Previous studies have shown that the variants of CUB and sushi multiple domains 1 (CSMD1) demonstrate significant genome-wide association with SCZ. However, few studies have been conducted on the effect of antipsychotics on the expression levels of CSMD1. This study explored whether a change occurs in the expression of the CSMD1 gene before and after antipsychotic treatment in SCZ patients.MethodsThe study population comprised Han Chinese patients from eastern China, including 32 SCZ patients and 48 healthy controls. The expression of CSMD1 before and after treatment in the SCZ group and between the two groups was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR).ResultsThe expression levels of the CSMD1 gene in the peripheral blood mononuclear cells (PBMCs) of SCZ patients were lower than those in the healthy controls. The expression levels of the CSMD1 gene in the PBMCs of the SCZ patients after antipsychotic treatment were higher than those in the baseline SCZ patients (all P < 0.05).ConclusionsOur results showed that the expression levels of CSMD1 are correlated with the development and treatment of SCZ, providing further evidence for the involvement of CSMD1 in SCZ.
| S-EPMC6466712 | biostudies-literature
Project description:BackgroundSchizophrenia is a severe, heritable, and refractory psychiatric disorder. Several studies have shown that the disrupted in schizophrenia 1 (DISC1) gene is closely associated with schizophrenia by its role in neuronal morphology, synaptic function, brain development, and dopamine homeostasis etc. This study intended to investigate the expression levels of DISC1 gene in schizophrenia patients compared with healthy controls, and the expression variation of DISC1 gene before and after antipsychotic treatment in schizophrenia patients.MethodsIn this study, we compared DISC1 expression levels in blood of 48 healthy controls, and 32 schizophrenia patients before and after 12 weeks of antipsychotic treatment using real-time quantitative PCR (RT-qPCR) analysis.ResultsThe expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients before antipsychotic treatment were higher than those in healthy controls (P < 0.01); whereas after antipsychotic treatment, the expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients still remained increased (P < 0.01).ConclusionsOur study provided further support for the involvement of DISC1 in the development of schizophrenia.
| S-EPMC7532617 | biostudies-literature
Project description:Severe immunosuppression is a hallmark of Morbillivirus infections. To study the underlying mechanisms, we have developed a ferret model of canine distemper virus infection. The model reproduces all clinical signs of measles, but the lack of ferret-specific reagents has limited the characterization of the cellular immune response. Towards this, we cloned ferret cytokines and established semi-quantitative real-time PCR assays. To demonstrate the utility of these assays we compared the cytokine profiles elicited by lethal and non-lethal strains during the prodromal phase. We observed a general lack of cytokine induction in animals that later succumbed to the disease, whereas survivors mounted a robust and sustained response. The newly developed cytokine assays strengthen and expand the ferret model not only for Morbillivirus pathogenesis studies but also for several other human respiratory viruses including influenza and SARS.
| S-EPMC2697062 | biostudies-literature
Project description:MicroRNAs (miRNAs) are potent regulators of gene expression with proposed roles in brain development and function. We hypothesized that miRNA expression profiles are altered in individuals with severe psychiatric disorders.With real-time quantitative polymerase chain reaction, we compared the expression of 435 miRNAs and 18 small nucleolar RNAs in postmortem brain tissue samples from individuals with schizophrenia, individuals with bipolar disorder, and psychiatrically healthy control subjects (n = 35 each group). Detailed demographic data, sample selection and storage conditions, and drug and substance exposure histories were available for all subjects. Bayesian model averaging was used to simultaneously assess the impact of these covariates as well as the psychiatric phenotype on miRNA expression profiles.Of the variables considered, sample storage time, brain pH, alcohol at time of death, and postmortem interval were found to affect the greatest proportion of miRNAs. Of miRNAs analyzed, 19% exhibited positive evidence of altered expression due to a diagnosis of schizophrenia or bipolar disorder. Both conditions were associated with reduced miRNA expression levels, with a much more pronounced effect observed for bipolar disorder.This study suggests that modest underexpression of several miRNAs might be involved in the complex pathogenesis of major psychosis.
| S-EPMC3038345 | biostudies-literature
Project description:ObjectiveTo identify differences in peripheral blood gene expression between patients with different subclasses of juvenile idiopathic arthritis (JIA) and healthy controls in a multicenter study of patients with recent-onset JIA prior to treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents.MethodsPeripheral blood mononuclear cells (PBMCs) from 59 healthy children and 136 patients with JIA (28 with enthesitis-related arthritis [ERA], 42 with persistent oligoarthritis, 45 with rheumatoid factor [RF]-negative polyarthritis, and 21 with systemic disease) were isolated from whole blood. Poly(A) RNA was labeled using a commercial RNA amplification and labeling system (NuGEN Ovation), and gene expression profiles were obtained using commercial expression microarrays (Affymetrix HG-U133 Plus 2.0).ResultsA total of 9,501 differentially expressed probe sets were identified among the JIA subtypes and controls (by analysis of variance; false discovery rate 5%). Specifically, 193, 1,036, 873, and 7,595 probe sets were different in PBMCs from the controls compared with those from the ERA, persistent oligoarthritis, RF-negative polyarthritis, and systemic JIA patients, respectively. In patients with persistent oligoarthritis, RF-negative polyarthritis, and systemic JIA subtypes, up-regulation of genes associated with interleukin-10 (IL-10) signaling was prominent. A hemoglobin cluster was identified that was underexpressed in ERA patients but overexpressed in systemic JIA patients. The influence of JAK/STAT, ERK/MAPK, IL-2, and B cell receptor signaling pathways was evident in patients with persistent oligoarthritis. In systemic JIA, up-regulation of innate immune pathways, including IL-6, Toll-like receptor/IL-1 receptor, and peroxisome proliferator-activated receptor signaling, were noted, along with down-regulation of gene networks related to natural killer cells and T cells. Complement and coagulation pathways were up-regulated in systemic JIA, with a subset of these genes being differentially expressed in other subtypes as well.ConclusionExpression analysis identified differentially expressed genes in PBMCs obtained early in the disease from patients with different subtypes of JIA and in healthy controls, providing evidence of immunobiologic differences between these forms of childhood arthritis.
| S-EPMC2782469 | biostudies-literature