Antipsychotic-induced epigenomic reorganization in frontal cortex samples from individuals with schizophrenia
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ABSTRACT:
PROVIDER: PRJNA729777 | ENA |
REPOSITORIES: ENA
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Project description:We examined the effects of antipsychotic medications on the cell-specific epigenomics and transcriptomics in the frontal cortex of schizophrenic subjects.
2021-11-05 | GSE174407 | GEO
Project description:Antipsychotic drugs are classified as typical and atypical based on extrapyramidal effects. However, since the frontal cortex is one of the most important regions for antipsychotic actions, this study attempted to classify antipsychotic drugs based on gene expression in the frontal cortex. Chlorpromazine and thioridazine were selected as typical antipsychotics, and olanzapine and quetiapine as atypical antipsychotics. Since these drugs have similar chemical structures, the effect of the basic structure on gene expression can be eliminated. Cluster analysis of microarray experiments showed thioridazine and olanzapine constituted a robust cluster. K-means clustering separated 4-drug-administered mice into chlorpromazine-quetiapine and thioridazine-olanzapine groups. This classification scheme is different from that which is based on criteria currently used to group the typical and atypical drugs and suggests that antipsychotic drugs can be further separated into multiple groups. Keywords: repeat sample
2004-09-24 | GSE1501 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE38481: A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes [HumanRef-8 v3.0] GSE38484: A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes [HumanHT-12 V3.0] Refer to individual Series
2012-07-08 | E-GEOD-38485 | biostudies-arrayexpress
Project description:Multiple studies have shown that brain gene expression is disturbed in subjects suffering from schizophrenia. However, disentangling disease effects from alterations caused by neuroleptics is a challenging task. <br> To address the issues of disease heterogeneity and the effect of antipsychotic medication, we use a large collection of 110 brain autopsy samples, subdivided according to the type of antipsychotic medication received. We use global and high-resolution mRNA quantification techniques to analyse gene expression in brain tissues. We also analyse transcription in-vitro, in cell lines before and after treatment with cytokines.<br> Results. We show that inflammation-related genes are up regulated in all groups of patients, including those not treated at the time of death. In particular, four co-expressed genes that are inducible by inflammatory cytokines showed increased mRNA levels, namely IFITM2, IFITM3, SERPINA3, and GBP1 (p-values from qPCR ? 0.01). We also show that these genes are expressed in oligodendrocyte and endothelial cell lines, and transcription is inducible by inflammatory cytokines in both cell lines. Our results give molecular support to the inflammatory theory of schizophrenia and suggest that inflammatory cytokines may stimulate transcription in endothelial brain cells during schizophrenia progression. Unexpectedly, inflammation-related genes may also have a role in myelin producing cells, since they are also inducible by cytokines in oligodendrocyte cell lines. Our findings encourage future research to explore whether anti-inflammatory agents can be used in combination with traditional antipsychotics for a more efficient treatment of schizophrenia.
2007-12-06 | E-MEXP-857 | biostudies-arrayexpress
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
2008-06-12 | E-GEOD-4031 | biostudies-arrayexpress
Project description:Background. Schizophrenia is an idiopathic psychiatric disorder with a high degree of polygenicity. Evidence from genetics, single-cell, and pharmacological studies suggest an important overlap between genes involved in the etiology of schizophrenia and the cellular mechanisms of action of antipsychotics in medium spiny neurons (MSNs). Methods. We applied single-cell RNA-sequencing to striatal samples from C57BL/6J mice chronically exposed to a typical antipsychotic (haloperidol), an atypical antipsychotic (olanzapine), or placebo. We implemented careful statistical analyses to identify differentially expressed genes in two cell populations identified from the single-cell RNA-sequencing (MSNs and microglia) and applied multiple analysis pipelines to contextualize these findings. Results. Differential expression analysis showed that there was a larger share of differentially expressed genes (DEGs) in MSNs from mice treated with olanzapine vs. haloperidol. DEGs were enriched in broad loci implicated by genetic studies of schizophrenia, and we highlighted nine genes with convergent evidence. Pathway analyses highlighted alternative splicing, mitochondrial function, and neuron and synapse development as particularly engaged by antipsychotics. In microglia, we identified pathways involved in microglial activation and inflammation as part of the antipsychotic response. Conclusions. Our goal was to evaluate connections between schizophrenia genetic findings and cellular gene expression changes following antipsychotic exposure. We found that differential gene expression in MSNs from mice chronically treated with olanzapine converges on similar pathways and gene sets.
2021-04-14 | GSE171977 | GEO
Project description:We have previously demonstrated functional and molecular changes in hippocampal subfields in individuals with schizophrenia (SZ) psychosis associated with hippocampal excitability. In this study, we use RNA-seq and assess global transcriptome changes in the hippocampal subfields, DG, CA3, and CA1 from individuals with SZ psychosis and controls to elucidate subfield-relevant molecular changes. We also examine changes in gene expression due to antipsychotic medication in the hippocampal subfields from our SZ ON- and OFF-antipsychotic medication cohort. We identify unique subfield-specific molecular profiles in schizophrenia postmortem samples compared to controls, implicating astrocytes in DG, immune mechanisms in CA3, and synaptic scaling in CA1. We show a unique pattern of subfield-specific effects by antipsychotic medication on gene expression levels with scant overlap of genes differentially expressed by SZ disease effect versus medication effect. These hippocampal subfield changes could provide the basis for previously observed hippocampal SZ pathology and explain the lack of full efficacy of conventional antipsychotic medication on SZ symptomatology. With further characterization, the identified distinct molecular profiles of the DG, CA3, and CA1 in SZ psychosis may serve to identify potential hippocampal-based therapeutic targets.
2020-05-11 | GSE138082 | GEO
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.
2023-03-19 | E-MTAB-11921 | biostudies-arrayexpress
Project description:Four sets of six microarray experiments were conducted. Six individual RTT frontal cortices were co-hybridized with six individual control frontal cortices. For example, the frontal cortex of patient RTT1 was compared with the occipital cortex of RTT1. Additionally, where the frontal cortex of a RTT sample was compared to the frontal cortex of a control sample, the comparison between the occipital cortices was conducted between the same samples. For example RTT1 frontal cortex vs. Con4 frontal cortex, RTT1 occipital cortex vs. Con4 occipital cortex. Each experiment was repeated and the fluorescent cyanine dyes were reversed.
2010-03-07 | E-MEXP-2588 | biostudies-arrayexpress
Project description:The study is directed to understand the impact of antipsychotic drugs on miRNA expression in liver cell line model
2022-02-08 | E-MTAB-11458 | biostudies-arrayexpress