Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE77445 | GEO | 2016/03/16
SECONDARY ACCESSION(S): PRJNA310345
REPOSITORIES: GEO
Similar Datasets
Project description:DNA methylation likely plays a role in the regulation of human stress reactivity. In a genome-wide analysis of blood DNA methylation in 85 healthy individuals a locus in the Kit ligand (KITLG) gene (cg27512205) had the strongest association with cortisol stress reactivity (p=5.8x10-6). Replication was obtained in two independent samples, one using blood (N=45, p=0.001) and the other using buccal cells (N=255,p=0.004). KITLG methylation strongly mediated the relationship between childhood trauma and cortisol stress reactivity (32% mediation). Its genomic location (CpG island shore within an H3K27ac enhancer mark) provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability. Bisulphite converted DNA from whole blood of 85 healthy controls exposed to psychosocial stress task (TSST-G) was hybridised to the Illumina Infinium 450k Human Methylation Beadchip The DOI for this paper will be 10.1038/NCOMMS10967.
2016-03-16 | E-GEOD-77445 | biostudies-arrayexpress
Project description:To assess how different levels of stress exposure affect epigenetic regulation mechanisms in cattle, we investigated genome-wide DNA methylation in 20 Italian Red Pied dairy cows falling in the high- and low-variant tails of the distribution of milk cortisol concentration (MC), a neuroendocrine biomarker of stress in dairy cows, measured in 126 animals belonging to the same farm in the framework of the Gen2Phen Italian project. The ‘low-’ and ‘high-cortisol’ groups of animals had MC<370 pg/ml and>810 pg/ml, respectively. Their methylome was analysed by Reduced Representation Bisulfite Sequencing, which provides single-base resolution methylation profiles across the whole genome. To date, 20 animals (10 low- and 10 high-MC) have been sequenced. The two groups showed similar proportion of methylation at CpG sites, while they differed at non-CpG sites. Significant methylation changes were observed in 897 regions and 248 genes. KEGG and Gene Ontology (GO) pathway analyses indicated that these genes were mainly involved in immune regulatory pathways, glucocorticoids metabolism and nervous system functions. These preliminary results suggest that cortisol secretion in livestock is mediated by epigenetic regulation, provide target biomarkers to assess the effect of stress management procedures and candidate genes for the selection of stress-tolerant animals.
2020-09-30 | GSE146877 | GEO
Project description:Major Depression (MDD) is a prevalent psychiatric disorder and exposure to stress is robust risk factor for MDD. Clinical data and rodent models have indicated the negative impact of chronic stress induced hormones like cortisol on brain volume, memory, and cell metabolism. However, the cellular and transcriptomic changes that occur in the brain after prolonged exposure to cortisol are less understood. Furthermore, astrocyte-specific contribution to cortisol-induced neuropathology remains understudied. Here, we have developed an in vitro model of “chronic stress” using human induced pluripotent stem cell-derived astrocytes treated with cortisol for 7 days. Whole transcriptome sequencing reveals differentially expressed genes (DEGs) uniquely regulated in chronic cortisol compared to acute cortisol treatment. Utilizing this paradigm, we examined the stress response transcriptome of astrocytes generated from MDD patient iPSCs. MDD-specific DEGs related to GPCR ligand binding, synaptic signaling, and ion homeostasis. Together, these data highlight the unique role astrocytes play in the central nervous system and present interesting genes for future study into the relationship between chronic stress and MDD.
2022-10-04 | GSE178071 | GEO
Project description:Chronic early life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming we treated zebrafish embryos with 1 micromolar cortisol and examined the effects on larvae. Treated larvae had elevated whole-body cortisol and glucocorticoid signaling, and up-regulated genes associated with defense response and immune system processes. 6 samples total were analyzed. 3 DMSO controls, and 3 cortisol treated (1 micromolar).
2016-06-01 | E-GEOD-80221 | biostudies-arrayexpress
Project description:Chronic early life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming we treated zebrafish embryos with 1 micromolar cortisol and examined the effects on larvae. Treated larvae had elevated whole-body cortisol and glucocorticoid signaling, and up-regulated genes associated with defense response and immune system processes.
2016-06-01 | GSE80221 | GEO
Project description:Cortisol administration during late gestation in ewes, modeling maternal stress, resulted in transcriptomic changes suggesting altered maturation and metabolic changes to the offspring heart. This study investigates the effects of cortisol on epicardial adipose tissue (EAT), a visceral fat pad associated with adverse cardiovascular conditions in adults. Pregnant ewes were treated with either 1 or 0.5 mg/kg/day cortisol from 115 days gestation to term and EAT collected from term fetuses (control: n=8, maternal cortisol 1 mg/kg/day: n=6) or two-week-old lambs (control: n=7, maternal cortisol 0.5mg/kg/day: n=9). Transcriptomic modeling was used to identify pathways altered by maternal cortisol over-exposure. Transcriptomic modeling confirmed the brown fat phenotype of EAT at term and a transition towards white fat at two weeks of age in EAT of control fetuses/lambs, and highlighted a role of immune responses, including complement-coagulation, and serotonin in this transition. Maternal cortisol (1mg/kg/day) increased the lipid peroxidation product 4-hydroxynonenal in EAT of term fetuses, but did not affect the number of activated macrophages or size of the lipid droplets in the depot; transcriptomics suggested an earlier metabolic maturation of EAT via, in part, increased immune responses. Conversely the transcriptomics in EAT of two-week-old lambs of ewes treated with a lower dose of cortisol (0.5mg/kg/day) suggested decreased metabolism of several substrates through both mitochondrial and cytosolic actions, and delayed maturation of EAT associated with a longer period of adipogenesis and angiogenesis.
2019-07-10 | GSE119254 | GEO
Project description:Transcriptional profiling of log and stationary phases of S. Typhimurium, comparing untreated controls with cortisol-treated samples. Each array used labelled cDNA against a common genomic DNA reference. Triplicate arrays were carried out for each of the 4 conditions: untreated log phase, untreated stationary phase, cortisol treated log phase and cortisol treated stationary phase.
2011-07-25 | E-GEOD-30923 | biostudies-arrayexpress
Project description:Previous studies have suggested that increases in maternal cortisol or maternal stress in late pregnancy increase the risk of stillbirth at term. In an ovine model with increased maternal cortisol over the last 0.20 of gestation, we have previously found evidence of disruption of fetal serum and cardiac metabolomics, and of expression of genes related to mitochondrial function and metabolism in biceps femoris, diaphragm and cardiac muscle. The present studies were designed to test for effects of chronically increased maternal cortisol on gene expression and metabolomics in placentomes near term. We hypothesized that changes in placenta may underlie or contribute to the alterations in fetal serum metabolomics, and thereby contribute to changes in striated muscle metabolism. Multi-omic analysis indicates that amino acid metabolism, particularly of branched chain amino acids and glutamate occur in placenta; changes in amino acid metabolism, degradation or biosynthesis in placenta were consistent changes in valine, isoleucine, leucine and glycine in fetal serum. The analysis also indicates changes in glycerophospholipid metabolism, and suggests changes in ER stress and antioxidant status in the placenta. These findings suggest that changes in placental function occurring with excess maternal cortisol in late gestation may contribute to metabolic dysfunction in the fetus at birth.
2020-09-01 | GSE149402 | GEO
Project description:We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol result in fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies in which we extended the duration of cortisol infusion (1mg/kg/d) to term, we found a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol and associated maternal hyperglycemia. To investigate the effects on the heart, transcriptomic analyses were performed on the septa using ovine microarrays and Webgestalt and Cytoscape programs for pathway inference. Analyses of the effects of 10 days of maternal cortisol infusion (130d-cortisol vs 130d control), ~25 days (term at ~140d-cortisol vs 140d control), normal maturation (140d-control vs 130d control) were performed. In all analyses gene ontology (GO) terms related to immune function and cytokine actions were significantly over-represented. After 10 days of cortisol, growth factor and muscle cell apoptosis pathways were significantly over-represented, consistent with our previous findings. We found significantly differentially regulated genes in the term fetuses (ie after ~25 days of cortisol) in pathways consistent with altered metabolism in the heart, particularly in mitochondria, associated with responses to hypoxia and to nutrient. Analysis of mitochondrial number by quantitative real-time PCR confirmed a significant decrease. These pathways were different from those modeled following the normal increase in cortisol in late gestation which contributes to normal maturation of the heart, and thus may be indicative of the fetal heart pathophysiologies seen in pregnancies complicated by diabetes, CushingM-bM-^@M-^Ys disease and chronic stress. 2 cohorts of singleton sheep fetuses at 129-131d gestation or 139-144d gestation (approximately term) were used. The first cohort received maternal cortisol infusion of 1mg/kg/day or vehicle for 10 days until approximately day 130 of gestation (n=6/group), the second cohort received the same dose of cortisol for approximately 25 days until near term (n=7, cortisol; n=7ewes, n=8 fetuses due to one set of twins, control)
2014-08-07 | E-GEOD-54237 | biostudies-arrayexpress
Project description:We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol result in fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies in which we extended the duration of cortisol infusion (1mg/kg/d) to term, we found a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol and associated maternal hyperglycemia. To investigate the effects on the heart, transcriptomic analyses were performed on the septa using ovine microarrays and Webgestalt and Cytoscape programs for pathway inference. Analyses of the effects of 10 days of maternal cortisol infusion (130d-cortisol vs 130d control), ~25 days (term at ~140d-cortisol vs 140d control), normal maturation (140d-control vs 130d control) were performed. In all analyses gene ontology (GO) terms related to immune function and cytokine actions were significantly over-represented. After 10 days of cortisol, growth factor and muscle cell apoptosis pathways were significantly over-represented, consistent with our previous findings. We found significantly differentially regulated genes in the term fetuses (ie after ~25 days of cortisol) in pathways consistent with altered metabolism in the heart, particularly in mitochondria, associated with responses to hypoxia and to nutrient. Analysis of mitochondrial number by quantitative real-time PCR confirmed a significant decrease. These pathways were different from those modeled following the normal increase in cortisol in late gestation which contributes to normal maturation of the heart, and thus may be indicative of the fetal heart pathophysiologies seen in pregnancies complicated by diabetes, Cushing’s disease and chronic stress.
2014-08-07 | GSE54237 | GEO