Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA289137 | ENA |
REPOSITORIES: ENA
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Project description:Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross-talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. Here, we investigated neuroendocrine as well as genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal (HPA) axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed a larger stress-induced increase of cardinal pro-inflammatory transcripts IL6 and FOSB, and an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups. Noteworthy, FKBP5 expression was less responsive to cortisol induction in the early adversity group, with potential effects on the ultra-short feedback loop that balances FKBP5 and glucocorticoid receptor activity. Further exploratory analyses showed differential stress-induced regulation of gene transcription between the groups. Prominent among the differentially regulated transcripts were those coding for genes involved in signal transducer activity, G-protein coupled receptors, and several genes involved in serotonin receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress responsive pathways, which - when chronically or repeatedly activated - might predispose individuals to stress-related psychopathology.
2015-11-30 | GSE70603 | GEO
Project description:Transgenerational effects of early experience on behavioural, hormonal and gene expression responses to acute stress in the precocial chicken. The data for the parental stressed and control birds is available in ArrayExpress with accession E-MTAB-924, while this experiment only concerns their offspring that never been exposed to early life stress.
2012-01-02 | E-MTAB-925 | biostudies-arrayexpress
Project description:Early-life adversity is an important risk factor for major depressive disorder (MDD) and schizophrenia (SCZ) that interacts with genetic factors to confer disease risk through mechanisms that are still insufficiently understood. One downstream effect of early-life adversity is the activation of glucocorticoid receptor (GR)-dependent gene networks that drive acute and long-term adaptive behavioral and cellular responses to stress. We have previously shown that genetic variants that moderate GR-induced gene transcription (GR-response eSNPs) are significantly enriched among risk variants from genome-wide association studies (GWASs) for MDD and SCZ. Here, we show that the 63 transcripts regulated by these disease-associated functional genetic variants form a tight glucocorticoid-responsive co-expression network (termed GCN). We hypothesized that changes in the correlation structure of this GCN may contribute to early-life adversity-associated disease risk. Therefore, we analyzed the effects of different qualities of social support and stress throughout life on GCN formation across distinct brain regions using a translational mouse model. We observed that different qualities of social experience substantially affect GCN structure in a highly brain region-specific manner. GCN changes were predominantly found in two functionally interconnected regions, the ventral hippocampus and the hypothalamus, two brain regions previously shown to be of relevance for the stress response, as well as psychiatric disorders. Overall, our results support the hypothesis that a subset of genetic variants may contribute to risk for MDD and SCZ by altering circuit-level effects of early and adult social experiences on GCN formation and structure.
2020-04-22 | GSE149074 | GEO
Project description:Transgenerational effects of early experience on behavioural, hormonal and gene expression responses to acute stress in the precocial chicken. The data for the offspring of the birds in this experiment is available in ArrayExpress with accession E-MTAB-925.
2012-01-02 | E-MTAB-924 | biostudies-arrayexpress
Project description:Early life social experiences are believed to confer persistent effects on individual’s biology and subsequent functioning and health. Using a diverse, longitudinal community sample of 178 children, we show that three different types of early life social experience: family income, parental education, and family psychosocial adversity, each predict DNA methylation within buccal epithelial cells. Each predictor was significantly associated with DNA methylation within a unique set of genomic CpG sites, with income showing the greatest number of associations. Findings were independently verified using pyrosequencing. Our results provide evidence for longitudinal associations between early life social environment and variation in DNA methylation during childhood, after adjusting for genetic ancestry and self-reported ethnic minority status. Gene ontology analyses of top, differentially methylated CpG sites point to genes serving immune and developmental regulation functions, suggesting potential pathways for the biological embedding of early life stress and its association with later development and health.
2018-12-07 | GSE94734 | GEO
Project description:Research shows that children who are reared in households with low socioeconomic status are more vulnerable to heart disease, respiratory infection, and some cancers when they reach adulthood. This study conducted transcriptional profiling of PBMC in healthy adults who were low vs. high in early-life SES to explore the long-lasting genomic effects of early experience. Keywords: life stress, gene expression, inflammation, socioeconomic status Samples from 30 adults with low early-life SES and 30 adults with high early-life SES
2009-03-10 | E-GEOD-15180 | biostudies-arrayexpress
Project description:Transgenerational effects of early experience on behavioural, hormonal and gene expression responses to acute stress in the precocial chicken. The present accession presents the data from the adult chicken of the first (parental) generation.To access data for the young chicken of the first (parental) generation see accession E-MTAB-924. The male offspring of the birds of the first (parental) generation is also available in ArrayExpress with accession E-MTAB-925.
2015-03-12 | E-MTAB-3319 | biostudies-arrayexpress
Project description:The risk for psychiatric disorders is strongly affected by environmental stressors. The underlying mechanisms are inevitably multifactorial still not fully understood. Glucocorticoids (GCs), which are prominent stress mediators that affect transcriptional activity and brain morphology, are implicated in the pathophysiology of multiple forms of psychopathology. The challenge is that of establishing the relevance of GC-related transcriptional effects for stress-related psychopathology in humans. We addressed this issue by generating gene expression data from hippocampal dentate gyrus from macaques and rats to identify clusters of co-expressed genes sensitive to GC exposure as the basis for a biologically-informed polygenic risk score (ePRS) to investigate neuropsychiatric outcomes in humans exposed to early life adversity. We used RNA-sequencing data to identify a cluster of GC-responsive genes co-expressed in the posterior dentate gyrus (pDG) of female Cynomologus monkeys and preserved in the rat model with the homologous region (the dorsal DG). In total 11395 SNPs derived from these genes (507 genes) were used to create an ePRS to explore the interaction with early life adversity on psychiatric phenotypes in human cohorts using the UK Biobank Resource and ALSPAC data sets. The biologically-informed ePRS significantly predicted psychotic behavior in adversity-exposed females as well as variation in brain volume. These findings reveal that GC exposure influences a specific group of genes in pDG, largely enriched for transcription processes and pathways related to development activity. Variations in the expression of this gene network can be used in a translational manner to predict risk for neuropsychiatric conditions and brain volume alterations after early stress exposure. These results highlight the importance of hippocampal GC-related transcriptional activity as a mediator for the effects of early life adversity on mental health outcomes.
2020-05-29 | GSE151342 | GEO
Project description:Epigenetic Vestiges of Early Developmental Adversity: Child Stress Exposure and Adolescent DNA Methylation
| PRJNA135879 | ENA
Project description:Discrimination is a type of social adversity defined as unfair treatment and prejudice against individuals due to membership of a specific group. Discrimination has been linked to several age-related outcomes such as cognitive decline, inflammation, and cardiovascular disease. However, the molecular drivers to these observations are poorly understood. Social adverse factors have been associated with proinflammatory and interferon gene expression, a phenomenon described as Conserved Transcriptome Response to Adversity. It is not known whether there are additional genes whose transcription is associated with exposure to discrimination among both African American and White adults. In this study, we have examined how perceived discrimination in African American and White adults affects genome-wide transcriptome differences using RNA sequencing. Perceived discrimination was measured based on responses to lifetime discrimination and racial discrimination questionnaires. Differential gene expression and pathway analysis was conducted in a cohort (N=59) stratified by race, sex, and discrimination exposure. We found that there were 28 significantly differentially expressed genes associated with high discrimination exposure in African American adults when compared to White adults with high discrimination exposure. The most significantly upregulated genes among African Americans with high discrimination exposure were related to immune function immunoglobulin lambda variable 2-11 (IGLV2-11), S100 calcium binding protein B (S100B), immunoglobulin kappa variable 3-20 (IGKV3-20), immunoglobulin kappa variable 4-1 (IGKV4-1); the most significantly downregulated genes were associated with immune modulation and cancer, lung cancer associated transcript 1 (LUCAT1), thrombospondin 1 (THBS1), and actin related protein 2/3 complex inhibitor (ARPIN). In addition, the most significantly upregulated Gene Ontology (GO) biological process among African American men with high exposure to discrimination compared to White male adults with high exposure to discrimination was regulation of cytokine biosynthetic processes. Conversely, immune response was the most significantly downregulated GO biological process among African American women with high discrimination exposure compared White women with high discrimination exposure. Understanding the biological pathways through which adverse social factors like discrimination affect gene expression will be critical in advancing knowledge of age-related health disparities.
2025-03-12 | GSE244654 | GEO