Cell-type specific transcriptomics of the the dlPFC in females with MDD [single-nucleus RNA-seq]
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PROVIDER: PRJNA883411 | ENA |
REPOSITORIES: ENA
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Project description:We performed high-throughput snRNA-seq using the 10X Genomics Chromium platform on archived post-mortem dorsolateral prefrontal cortex (BA9) tissue in female MDD subjects who died by suicide and in female control subjects to identify cell-type specific differentially expressed genes. We further re-processed in parallel a previously generated snRNA-seq dataset in males with or without MDD to generate comparable differential expression results and compare the cell-type specific MDD-associated differences between the sexes.
2023-04-24 | GSE213982 | GEO
Project description:Background: Major Depressive Disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for MDD suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesized that regulatory genomic processes are involved in the pathology of both MDD and suicidality. Methods: Genome-wide patterns of DNA methylation were assessed in depressed MDD suicide completers (n=20) and compared to non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focussed on identifying differentially methylated regions (DMRs) associated with suicidal depression, and epigenetic variation was explored in the context of polygenic risk scores for major depression and MDD suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed MDD suicide completers and polygenic burden for MDD and MDD suicide attempt. Results: We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite-pyrosequencing and replicated in a second set of MDD suicide samples, which is characterized by significant hypomethylation in both cortical brain regions in MDD MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for MDD suicide attempt, but not major depression. MDD suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Conclusions: Our data suggest there are coordinated changes in DNA methylation associated with MDD suicide that may offer novel insights into the molecular pathology associated with depressed MDD suicide completers.
2016-11-01 | GSE88890 | GEO
Project description:Rational: Major depressive disorder (MDD) is a leading cause of disease burden worldwide. While the incidence, symptoms and treatment of MDD all point toward major sex differences, the molecular mechanisms underlying this sexual dimorphism remain largely unknown. Methods: Here, combining differential expression and gene coexpression network analyses, we provide a comprehensive characterization of male and female transcriptional profiles associated with MDD across 6 brain regions. We overlap our human profiles with those from a mouse model of chronic variable stress and capitalize on converging pathways to define molecular and physiological mechanisms underlying the expression of stress susceptibility in males and females. Results: Our results show a major rearrangement of transcriptional patterns in MDD, with limited overlap between males and females, an effect seen in depressed humans and in stressed mice. We identify key regulators of sex-specific gene networks underlying MDD and confirm their sex-specific impact as mediators of stress susceptibility. For example, downregulation of the female-specific hub gene DUSP6 in prefrontal cortex mimics stress susceptibility in females only by increasing ERK signaling and pyramidal neuron excitability. Such DUSP6 downregulation also recapitulates the transcriptional remodeling that occurs in PFC of depressed females. Conclusions: Together, our findings reveal dramatic sexual dimorphism at the transcriptional level in MDD and highlight the importance of studying sex-specific treatments for this disorder.
2017-08-12 | GSE102556 | GEO
Project description:This article presents a study that examines the proteomic alterations associated with opioid use disorder (OUD) in the human brain. The study investigates the interplay between pro-inflammatory signaling, extracellular matrix (ECM) remodeling, and synaptic plasticity in the corticostriatal circuitry associated with OUD. The findings reveal differential alterations in the synaptic proteomes across the nucleus accumbens (NAc) and dorsolateral prefrontal cortex (DLPFC), indicating that changes in certain synaptic subtypes are unique to each brain region. The proteomic alterations associated with OUD in DLPFC are mainly in glutamatergic, serotonergic, dopaminergic, and oxytocin signaling, while altered adrenergic signaling is enriched in NAc. The study also identifies alterations in proteins involved in circadian entrainment specifically in synaptic enrichments in both DLPFC and NAc of OUD subjects. These findings provide new evidence linking disrupted molecular rhythms in the regulation of distinct synaptic subtypes altered by opioids.
2023-10-25 | PXD041333 | Pride
Project description:A cardinal symptom of Major Depressive Disorder (MDD) is the disruption of circadian patterns. Yet, to date, there is no direct evidence of circadian clock dysregulation in the brains of MDD patients. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain was difficult to characterize. Here we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-hour cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses ('Controls') and 34 MDD patients. Our dataset covered ~12,000 transcripts in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (AnCg), hippocampus (HC), amygdala (AMY), nucleus accumbens (NAcc) and cerebellum (CB). Several hundred transcripts in each region showed 24-hour cyclic patterns in Controls, and >100 transcripts exhibited consistent rhythmicity and phase-synchrony across regions. Among the top ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERB), DBP, BHLHE40(DEC1), and BHLHE41(DEC2). The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in MDD brains, due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This is the first transcriptome-wide analysis of cyclic patterns in the human brain and demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggest novel molecular targets for treatment of mood disorders. Sample collection, including human subject recruitment and characterization, tissue dissection, and RNA extraction, was described previously (see Evans 2003 Neurobiol Dis 14:240-250, Li 2004 Biol Psychiatry 55:346-352). RNA samples for different regions came from the same set of brains from 86 control subjects. Sample size varied by region: AnCg (n=70 controls), DLPFC (n=83), CB (n=51), AMY (n=32), HC (n=63) and NAcc (n=66). Many of the samples were run on two or more chips, resulting in the following chip counts for each region: AnCg = 124, DLPFC = 161, CB = 79, AMY = 62, HC = 108 and NaCC = 136. We ran each sample on at least two microarrays using the Affymetrix U133-A or U133Plus-v2 GeneChips, however, we only used the U133A part of the U133Plus-v2 GeneChip in our analysis. We applied RMA (Robust Multi-array Analysis) (see Irizarry 2003 Biostatistics 4:249-264, Irizarry 2003 Nucleic Acids Res 31:e15) to summarize probe set expression levels, using a custom Chip Definition File, resulting in expression data for 11,911 ENTREZ transcripts. Microarray data for each region were analyzed separately. All downstream analyses were performed in R. Details of the data processing, including data cleaning and normalization, are located in the Supplementary Materials (section 1). After data filtering, 1,424 microarrays remained, corresponding to 776 unique RNA samples in six regions.
2013-04-20 | E-GEOD-45642 | biostudies-arrayexpress
Project description:We do this study to identify and validate the differentially expressed circRNAs in MDD patients and to evaluate their potential as diagnostic biomarkers and as novel therapeutic targets for MDD, to explore the potential clinical value and possible mechanism of circRNAs in MDD.
2022-03-21 | GSE190518 | GEO
Project description:Linking the evolution of the phenotype to the underlying genotype is a key aim of evolutionary genetics and is crucial to our understanding of how natural selection shapes a trait. Here we consider the genetic basis of sex allocation behaviour in the parasitoid wasp Nasonia vitripennis using a transcriptomics approach. Females allocate offspring sex in line with Local Mate Competition (LMC) theory. Female-biased sex ratios are produced when one or few females lay eggs on a patch. As the number of females contributing offspring to a patch increases, less female-biased sex ratios are favoured. We contrasted the transcriptomic responses of females as they oviposit under conditions known to influence sex allocation: foundress number (a social cue) and the state of the host (parasitised or not). We found, that when females encounter other females on a patch, or assess host quality with their ovipositors, the resulting changes in sex allocation is not associated with significant changes in whole-body gene expression. We also found that the gene expression changes produced by females, as they facultatively allocate sex in response to a host cue and a social cue, are very closely correlated. We expanded the list of candidate genes associated with oviposition behaviour in Nasonia, some of which may be involved in fundamental processes underlying the ability to facultatively allocate sex, including sperm storage and utilisation. 2 x 3 factorial design. Females were placed into 1 of 2 "foundress number" groups: 1) alone or 2) in the presence of 9 other females (co-foundresses). Females were further subdivided into host treatment groups: i) given no host, ii) given a fresh host and iii) given a pre-parasitised host. This gives a total of 6 possible treatment combinations. For each of these 6 groups, 7 pools of 10 females were sequenced giving 42 libraries altogether.
2015-11-11 | E-GEOD-74241 | biostudies-arrayexpress
Project description:Linking the evolution of the phenotype to the underlying genotype is a key aim of evolutionary genetics and is crucial to our understanding of how natural selection shapes a trait. Here we consider the genetic basis of sex allocation behaviour in the parasitoid wasp Nasonia vitripennis using a transcriptomics approach. Females allocate offspring sex in line with Local Mate Competition (LMC) theory. Female-biased sex ratios are produced when one or few females lay eggs on a patch. As the number of females contributing offspring to a patch increases, less female-biased sex ratios are favoured. We contrasted the transcriptomic responses of females as they oviposit under conditions known to influence sex allocation: foundress number (a social cue) and the state of the host (parasitised or not). We found, that when females encounter other females on a patch, or assess host quality with their ovipositors, the resulting changes in sex allocation is not associated with significant changes in whole-body gene expression. We also found that the gene expression changes produced by females, as they facultatively allocate sex in response to a host cue and a social cue, are very closely correlated. We expanded the list of candidate genes associated with oviposition behaviour in Nasonia, some of which may be involved in fundamental processes underlying the ability to facultatively allocate sex, including sperm storage and utilisation.
2015-11-11 | GSE74241 | GEO
Project description:We examined the genetic profile of postmortem brain (hippocampal) samples; 15 brains from patients diagnosed with MDD were matched to brains from healthy subjects based on gender, race and age. Gene expression profiles in the dentate gyrus and CA1 subregions of the hippocampus were assessed by cDNA hybridization to 48K human HEEBO whole genome microarrays (Microarray, Inc). Two-group comparison: MDD (13 male, 8 female) vs. Control (11 male, 7 female). Dentate Gyrus (DG): 15 pairs of samples (1 array per pair); CA1: 15 pairs of samples (1 array per pair). Biological replicates. We can not provide a list of normalized values for each individual hybridization (per chip), but rather have a list of average expression values for all hybridizations used in the experiment (n=15). See supplementary files below. CODES: AAm, African American; C, Caucasian; CO, carbon monoxide; CVD, cardiovascular disease; ETOH, ethanol; F, female; Hx, history of alcohol abuse but not currently active; M, male; MDD, Major Depressive disorder, ND, no psychotropic medication detected; NOS, not otherwise specified, OD, drug overdose; PE, prior episode of major depression with psychotic features; PMI, postmortem interval (hours); SIGSW, self-inflicted gunshot wound; [1], Psychotrophic prescriptions within last month; [2], MDD in remission; [3], prescriptions for six days prior to death; *, samples present only in array sets for the dentate gyrus; **, samples present only in array sets for CA1.
2010-10-17 | E-GEOD-24095 | biostudies-arrayexpress
Project description:Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC
2021-06-12 | GSE174409 | GEO