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Immunological subtypes of depression: insights from monocyte gene expression II

ABSTRACT: Immunological subtypes of depression: insights from monocyte gene expression II

PROVIDER: PRJNA615653 | ENA |

REPOSITORIES: ENA

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Immunological subtypes of depression: insights from monocyte gene expression

Project description:Immunological subtypes of depression: insights from monocyte gene expression

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Immunological subtypes of depression: insights from monocyte gene expression

Project description:32 genes of a previously established inflammation-related gene signature were assessed in 197 patients with MDD and 151 controls collected during the EU-MOODINFLAME project. Monocyte gene expression data were related to age, gender, BMI, depression severity, Childhood Adversity (CA), and Suicide Risk (SR) data studycenter 1

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Immunological subtypes of depression: insights from monocyte gene expression II

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Investigating the first genomic response to stress – insights into the etiology and pathophysiology of major depression

Project description:While exposure to adverse life events and subsequent dysregulation of the stress hormone response broadly confer risk for depression, the specific molecular mechanisms mediating this risk are poorly understood. Through pharmacologic activation of the stress hormone response in blood cells we demonstrate that common genetic variants in long-range enhancer elements moderate the immediate transcriptome response to stress, and that these genetic differences are associated with increased risk for depression in the context of early adversity. Using imaging genetics we then link these common risk variants with dysregulated amygdala reactivity, an important trigger of the stress hormone response. The transcripts regulated by these risk variants in peripheral blood were also responsive to stress and stress hormone receptor activation in murine brain. Network modeling approaches suggest that these differences in transcriptional activation may mediate stress-related risk for depression by altering a functional gene network related to proteasome degradation and synaptic plasticity. A Dexamethasone Suppression Test was performed in 160 male subjects. Baseline and stimulated (3 hours after 1.5 mg dexamethasone p.o.) whole blood samples were analyzed using Illumina Human HT-12 v3 arrays.

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Immunological Signatures Driving COVID-19 Severity in Ghanaians: Insights from Upper Airway Transcriptome Analysis

Project description:Immunological Signatures Driving COVID-19 Severity in Ghanaians: Insights from Upper Airway Transcriptome Analysis

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Major depression MDD suicide brain study

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.

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Functional evaluation of neutrophil of patients at high risk for infection treated with monocyte/ neutrophil apheresis

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Project description:Novel Long Noncoding RNA HEAT4 Affects Monocyte Subtypes, Reducing Inflammation and Promoting Vascular Healing

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