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Whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes.

ABSTRACT: We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide. We also explored the potential implication of the TGF-β signalling pathway in the pathogenesis of suicidal behaviour. To our best knowledge, this is the first study that uses whole-exome sequencing for the investigation of suicide.

PROVIDER: EGAS00001003081 | EGA |

REPOSITORIES: EGA

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Whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes

Project description:We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide. We also explored the potential implication of the TGF-β signalling pathway in the pathogenesis of suicidal behaviour. To our best knowledge, this is the first study that uses whole-exome sequencing for the investigation of suicide.

| EGAS00001002818 | EGA

Microarray profiling of PFC, HPC and STR from subjects with schizophrenia, bipolar, MDD or control

Project description:Schizophrenia is a complex psychiatric disorder encompassing a range of symptoms and etiology dependent upon the interaction of genetic and environmental factors. Several risk genes, such as DISC1, have been associated with schizophrenia as well as bipolar disorder (BPD) and major depressive disorder (MDD), consistent with the hypothesis that a shared genetic architecture could contribute to divergent clinical syndromes. The present study compared gene expression profiles across three brain regions in post-mortem tissue from matched subjects with schizophrenia, BPD or MDD and unaffected controls. Post-mortem brain tissue was collected from control subjects and well-matched subjects with schizophrenia, BPD, and MDD (n=19 from each group). RNA was isolated from hippocampus, Brodmann Area 46, and associative striatum and hybridized to U133_Plus2 Affymetrix chips. Data were normalized by RMA, subjected to pairwise comparison followed by Benjamini and Hochberg False Discovery Rate correction (FDR). Samples derived from patients with schizophrenia exhibited many more changes in gene expression across all brain regions than observed in BPD or MDD. Several genes showed changes in both schizophrenia and BPD, though the magnitude of change was usually larger in schizophrenia. Several genes that have variants associated with schizophrenia were found to have altered expression in multiple regions of brains from subjects with schizophrenia. Continued evaluation of circuit-level alterations in gene expression and gene-network relationships may further our understanding of how genetic variants may be influencing biological processes to contribute to psychiatric disease. Pre-frontal cortex, striatum and hippocampus were obtained from subjects with schizophrenia, bipolar disorder, major depressive disorder and matched controls.

2014-01-11 | E-GEOD-53987 | biostudies-arrayexpress

Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

Project description:Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder. Epigenetic study of MZ twins discordant for Major Depressive Disorder

2014-01-21 | E-GEOD-54222 | biostudies-arrayexpress

Comparison of brain and hippocampal majority proteomes from MAP6 KO mice submitted or not to electroconvulsive stimulations

Project description:For major depression, the non-drug therapy Electroconvulsive therapy (ECT) treatment is highly effective and fast-acting. Despite a large and long-standing clinical use, the neurobiological mechanisms underlining ECT curative action are still poorly understood. Thanks to a genetic animal model that constitutively exhibit behavioural and biological features relevant to some aspects of major depressive disorder, here we analyse the behavioural and biological consequences of electroconvulsive stimulations (ECS), the animal model of ECT. We found that a classical ECS treatment, with 10 stimulation over 2 weeks period, has a beneficial effect on constitutive behavioural defects. We therefore compared brain and hippocampal majority proteomes from MAP6 KO mice submitted or not to electroconvulsive stimulations.

2019-03-12 | PXD008543 | Pride

Prefrontal cortex microRNA expression profiling in major depression

Project description:To gain insight into the potential role of miRNA in major depressive disorder, in this study we assessed global expression of miRNAs in the ventrolateral prefrontal cortex (PFC) of depressed individuals in comparison to psychiatrically healthy controls. Our screening pointed to miR-1202, a miRNA specific to primates and enriched in the human brain. We validated our findings using quantitative real-time PCR and identified target genes of the differentially expressed miRNAs using bioinformatics analysis. MiR-1202 interacts with and regulates the expression of the metabotropic glutamate receptor 4 (GRM4) gene, and it responds to antidepressant treatment. These results suggest that miR-1202 is associated with the pathophysiology of depression, and is a potential target for novel antidepressant treatments.

2014-05-30 | GSE58105 | GEO

Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

Project description:Genome-wide MeDIP-Sequencing of 23 monozygotic twin pairs (n=46) from Australia discordant for major depressive disorder (MDD). MeDIP-seq of 23 monozygotic twin pairs discordant for major depressive disorder. MZ twin pairs were compared to identify significantly differently methylated sites associated with MDD.

2014-01-25 | E-GEOD-54370 | biostudies-arrayexpress

Blood transcriptomic markers in patients with late-onset major depressive disorder

Project description:Search for the biomarkers of major depressive disorder (MDD) has facilitated from the genes expressed in the patient’s blood cells. Because the severity of depressive symptoms and characteristics in patients with MDD are differed by the age at onset of first depressive episode, the potential transcriptomic markers in blood cells may also be different by the age at onset of MDD. In this study, we searched the transcriptomic markers of late-onset (onset ages ≥ 50 years) MDD (LOD) from the expressed genes in blood cells, and identified state-dependent biomarkers in the patients. We assessed the expressed genes in blood cells by the microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD.

2016-01-14 | GSE76826 | GEO

Protein coding Transcriptomic analysis in postmortem brain subjects for research with major depressive disorder and suicide

Project description:Protein coding Transcriptomic analysis in postmortem brain subjects for research with major depressive disorder and suicide

| PRJNA888192 | ENA

Blood transcriptomic markers in patients with late-onset major depressive disorder

Project description:Search for the biomarkers of major depressive disorder (MDD) has facilitated from the genes expressed in the patientâs blood cells. Because the severity of depressive symptoms and characteristics in patients with MDD are differed by the age at onset of first depressive episode, the potential transcriptomic markers in blood cells may also be different by the age at onset of MDD. In this study, we searched the transcriptomic markers of late-onset (onset ages â¥ 50 years) MDD (LOD) from the expressed genes in blood cells, and identified state-dependent biomarkers in the patients. We assessed the expressed genes in blood cells by the microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD. Elderly (age â¥50 years) outpatients and inpatients with MDD corresponding to a DSM-IV diagnosis of the melancholy type of MDD episodes were studied. The depressive state was measured using the Structured Interview Guide for the Hamilton Depression (SIGH-D) rating scale. Syndromal remission was defined as a stage in which a participant did not meet the diagnosis of a MINI major depressive episode for a period of 2 consecutive months and had a SIGH-D score of less than 8. Twelve healthy individuals were also recruited. Blood was obtained from the participants and analyzed using an Agilent SurePrint G3 Human GE 8Ã60K v2 Microarray (Design ID: 039494).

2016-01-14 | E-GEOD-76826 | biostudies-arrayexpress

Expression data from human brain amygdala - including control samples and samples with major depression disorders (42 samples MD3_AMY)

Project description:Major depressive disorder is a heterogeneous illness with a mostly uncharacterized pathology. Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases (See publication for details). 42 total samples in 21 pairs were analyzed in postmortem tissue from the amygdala.

2014-05-16 | E-GEOD-54564 | biostudies-arrayexpress

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