Project description:Schizophrenia (SZ) is a serious mental disorder that is typically treated with antipsychotic medication. Treatment-resistant schizophrenia (TRS) is the condition where symptoms remain after pharmacological intervention, resulting in long-lasting functional and social impairments. As the identification and treatment of a TRS patient requires previous failed treatments, early mechanisms of detection are needed in order to quicken the access to effective therapy, as well as improve treatment adherence. In this study, we aim to find a microRNA (miRNA) signature for TRS, as well as to shed some light on the molecular pathways potentially involved in this severe condition. To do this, we compared the blood miRNAs of schizophrenia patients that respond to medication and TRS patients, thus obtaining a 16-miRNA TRS profile. Then, we assessed the ability of this signature to separate responders and TRS patients using hierarchical clustering, observing that most of them are grouped correctly (~70% accuracy). We also conducted a network, pathway analysis, and bibliography search to spot molecular pathways potentially altered in TRS. We found that the response to stress seems to be a key factor in TRS and that proteins p53, SIRT1, MDM2, and TRIM28 could be the potential mediators of such responses. Finally, we suggest a molecular pathway potentially regulated by the miRNAs of the TRS profile.
Project description:Schizophrenia (SZ) is a serious mental disorder that is typically treated with antipsychotic medication. Treatment-resistant schizophrenia (TRS) is the condition where symptoms remain after pharmacological intervention, resulting in long-lasting functional and social impairments. As the identification and treatment of a TRS patient requires previous failed treatments, early mechanisms of detection are needed in order to quicken the access to effective therapy, as well as improve treatment adherence. In this study, we aim to find a microRNA (miRNA) signature for TRS, as well as to shed some light on the molecular pathways potentially involved in this severe condition. To do this, we compared the blood miRNAs of schizophrenia patients that respond to medication and TRS patients, thus obtaining a 16-miRNA TRS profile. Then, we assessed the ability of this signature to separate responders and TRS patients using hierarchical clustering, observing that most of them are grouped correctly (~70% accuracy). We also conducted a network, pathway analysis, and bibliography search to spot molecular pathways potentially altered in TRS. We found that the response to stress seems to be a key factor in TRS and that proteins p53, SIRT1, MDM2, and TRIM28 could be the potential mediators of such responses. Finally, we suggest a molecular pathway potentially regulated by the miRNAs of the TRS profile.
Project description:The study profiles genome-wide miRNA expression in blood from 15 early-onset SZ (EOS) cases and 15 healthy controls. A total of 1070 miRNAs were detected by the microarrays in our samples. We profiles miRNA expression in 15 schizophrenia samples and 15 healthy controls to explore the alteration of miRNAs in schizophrenia.
Project description:This study examined the miRNA expression level in exosomal derived from the plasma of first episode schizophrenia (FOS) patients and Healthy controls (HC), and explored the the potential of exosomes as biomarkers for schizophrenia. This study examined the lncRNA expression level in exosomal derived from the plasma of first episode schizophrenia (FOS) patients and Healthy controls (HC), and explored the the potential of exosomes as biomarkers for schizophrenia. This study examined the mRNA expression level in exosomal derived from the plasma of first episode schizophrenia (FOS) patients and Healthy controls (HC), and explored the the potential of exosomes as biomarkers for schizophrenia.
Project description:The miRNA microarray expression data used in this study was derived using the commercial BeadArray-based miRNA microarray platform (Illumina). The data set contained 211 RNA samples from peripheral blood mononuclear cells (PBMC) as described previously, including 128 schizophrenia subjects and 83 non-psychiatric controls. As each miRNA array matrix held 96 sample arrays, the samples were distributed into four array matrices.
Project description:In pevious research we have shown that the disruption of the normal development of the ventral hippocampus in rodents leads to cellular abnormalities in the frontal cortex and behavioral deficits related to schizophenia (Neurotox Res. 2002, 4(5-6):469-475). We propose the use of gene expression analysis to investigate the molecular underpinnings of these processes which may shed light on the molecular processes relevant to human schizophrenia. In addition, we seek to characterize expression differences induced by chronic administration of antipsychotic medications, which may give insight into the molecular processes involved in ameliorating psychotic symptoms. Using both surgical and drug interventions, we aim to examine experimentally induced expression differences in the rodent brain that are relevant to human neuropsychiatric disorders. Disruption of the normal development of the vental hippocampus or chronic neuroleptic administration, will result in gene expression changes in the frontal cortex of rats. Elucidation of the molecular cascades underlying these treatments will shed light on both the pathoetiology (from the lesion experiments) and theurapeutic processes (from the antipsychotic treatment experiments) involved in human schizophrenia. We have developed 3 groups of samples:; 1] Ventral hippocampal lesion in neonatal rats (treatment and controls, total N=22); 2] Tetrodotoxin disruption of the ventral hippocampus (treatment and controls, total N=20); 3] Chronic administration of neuroleptics (multiple drugs, multiple doses, and controls, total N=63) Grand Total N=105
Project description:Schizophrenia patients vary in their response to antipsychotic (AP) treatment and predicting if and which therapy will be efficient is of high clinical and social importance. Here, we set out to analyze blood methylomes of 28 schizophrenia patients just before starting (baseline) risperidone treatment and four weeks later (follow-up) in order to look for differences that may help predict variation in response. We were not able to identify CpGs whose baseline methylation could be used as a predictive biomarker, but our analysis suggests the role of methylation status of genes involved in immunity, neurotransmission and neuronal development in the treatment response.