Project description:Post-traumatic stress disorder (PTSD) can develop following severe trauma, but the extent to which genetic and environmental risk factors contribute to individual clinical outcomes is unknown. Here, we compared transcriptional responses to hydrocortisone exposure in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons and peripheral blood mononuclear cells (PBMCs) from combat veterans with PTSD (n = 19 hiPSC and n = 20 PBMC donors) and controls (n = 20 hiPSC and n = 20 PBMC donors). In neurons only, we observed diagnosis-specific glucocorticoid-induced changes in gene expression corresponding with PTSD-specific transcriptomic patterns found in human postmortem brains. We observed glucocorticoid hypersensitivity in PTSD neurons, and identified genes that contribute to this PTSD-dependent glucocorticoid response. We find evidence of a coregulated network of transcription factors that mediates glucocorticoid hyper-responsivity in PTSD. These findings suggest that induced neurons represent a platform for examining the molecular mechanisms underlying PTSD, identifying biomarkers of stress response, and conducting drug screening to identify new therapeutics.
Project description:PTSD - Posttraumatic stress disorder. 33 samples taken from PMBCs of survivors of psychological trauma, in two time points: in ER, few hours after the truma, and four months later. Some of the patients devepled chronic PTSD (17 samples) and others recovered and set to be the Control group (16 samples). This is the normalized active genes: 4512 probes from U95A chip. The raw data is available in series GSE845. Samples are labeled with 3 tags: P/C for PTSD or Control, ER/M4 - for time point of sample, D/ND for Decrement or Non-decrement symptoms over time. (e.g. sample 23C-M4-D-Norm was taken 4 months after trauma from patient 23 which belongs to the control group and showed decrease in symptoms) . Samples include the expression value, the GeneBank accession number and Affymetrix indication of valid calls. Keywords = PTSD Keywords = Normalized Keywords = PMBC Keywords: other
Project description:PTSD - Posttraumatic stress disorder. 33 samples taken from PMBCs of survivors of psychological trauma, in two time points: in ER, few hours after the truma, and four months later. Some of the patients devepled chronic PTSD (17 samples) and others recovered and set to be the Control group (16 samples). This is the raw data consists of 12,600 probes from U95A chip. Samples are labeled with 3 tags: P/C for PTSD or Control, ER/M4 - for time point of sample, D/ND for Decrement or Non-decrement symptoms over time. (e.g. sample 23C-M4-D was taken 4 months after trauma from patient 23 which belongs to the control group and showed decrease in symptoms) . Samples include the expression value, the GeneBank accession number and Affymetrix indication of valid calls. Keywords: other
Project description:Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We analyzed transcriptome-wide gene expression profiles of 149 UCB samples from neonates born to mothers with prenatal PTSD (n=20), depression (n=31) and PTSD with comorbid depression (PTSD/Dep; n=13), compared to neonates born to carefully matched trauma exposed controls without meeting PTSD criteria (TE; n=23) and healthy mothers (n=62). We also evaluated physiological and developmental measures in these infants at birth, six months and twenty-four months. A multistep analytic approach was used that specifically sought to: 1) identify dysregulated genes, molecular pathways and discrete groups of co-regulated gene modules in UCB associated with prenatal maternal psychopathologies; and 2) to determine the impact of perinatal PTSD and depression on early childhood development outcomes.
Project description:PTSD - Posttraumatic stress disorder. 33 samples taken from PMBCs of survivors of psychological trauma, in two time points: in ER, few hours after the truma, and four months later. Some of the patients devepled chronic PTSD (17 samples) and others recovered and set to be the Control group (16 samples). This is the normalized active genes: 4512 probes from U95A chip. The raw data is available in series GSE845. Samples are labeled with 3 tags: P/C for PTSD or Control, ER/M4 - for time point of sample, D/ND for Decrement or Non-decrement symptoms over time. (e.g. sample 23C-M4-D-Norm was taken 4 months after trauma from patient 23 which belongs to the control group and showed decrease in symptoms) . Samples include the expression value, the GeneBank accession number and Affymetrix indication of valid calls.
Project description:The gene expression approach has provided promising insights into the pathophysiology of PTSD. However, few studies used hypothesis-free transcriptome-wide expression approach. Transcriptome-wide expression study using RNA sequencing (RNA-Seq) of whole blood was conducted in 324 World Trade Center responders (201 with never, 81 current and 42 past PTSD). The current and never PTSD samples were randomly split to form both discovery (N=195) and replication (N=87) cohorts. Differentially expressed genes identified in RNA-Seq were used in pathway analysis and to create a polygenic expression score. There were 448 differentially expressed genes in the discovery cohort, of which 99 remained significant in the replication cohort, and 5 (FKBP5, NDUFA1, CCDC85B, SNORD54, SNORD46) showed >1.2-fold difference in expression consistently between the discovery and replication cohorts. Several enriched biological pathways were found, including glucocorticoid receptor signaling and immunity-related pathways, but were not significant following FDR correction. The gene expression score achieved sensitivity of 0.917 and specificity of 0.508 for identifying PTSD cases in the replication cohort. It was similar in current and past PTSD, with both groups scoring higher than trauma-exposed controls. We confirmed the role of FKBP5 in PTSD and identified four additional differentially expressed genes that may constitute biomarkers for this condition. Together with the pathway analysis results, these findings point to HPA-axis and immune dysregulation as key biological processes underpinning PTSD. A novel polygenic expression aggregate that differentiates PTSD patients from trauma-exposed controls might be a useful screening tool for research and clinical practice, if replicated in other populations.
Project description:We identified hyper- and hypo-methylated cytosine sites and genes genome-wide using bisulfite sequencing in comparison between PTSD and control group, and between Major Depressive Disorder (MDD) and control group,