Using Next-Generation Sequencing Transcriptomics to Determine Markers of Post-traumatic Symptoms - preliminary findings from a post-deployment cohort
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ABSTRACT:
PROVIDER: PRJNA430870 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6496850_1.fastq.gz | Fastqsanger.gz | |||
| SRR6496850_2.fastq.gz | Fastqsanger.gz | |||
| SRR6496860_1.fastq.gz | Fastqsanger.gz | |||
| SRR6496860_2.fastq.gz | Fastqsanger.gz | |||
| SRR6496870_1.fastq.gz | Fastqsanger.gz |
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Project description:Post-traumatic stress disorder is a concerning psycho behavioral disorder thought to emerge from the complex interaction between genetic and environmental factors. For soldiers exposed to combat, the risk of developing this disorder is two-fold and diagnosis is often late, when much sequela has set in. To be able to identify and diagnose in advance those at “risk” of developing PTSD, would greatly taper the gap between late sequelae and treatment. Therefore, this study sought to test the hypothesis that the transcriptome can be used to track the development of PTSD in this unique and susceptible cohort of individuals. Gene expression levels in peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms) were determined by RNA sequencing technology following their return from deployment to Afghanistan. Count-based gene expression quantification, normalization and differential analysis (with thorough correction for confounders) revealed significant differences in two genes, LRP8 and GOLM1 . These preliminary results provide a proof-of-principle for the diagnostic utility of blood-based gene expression profiles for tracking symptoms of post-traumatic stress disorder in soldiers returning from tour. It is also the first to report transcriptome-wide expression profiles alongside a post-traumatic symptom checklist.
2019-01-18 | GSE109409 | GEO
Project description:Post-traumatic stress disorder is a concerning psychobehavioral disorder thought to emerge from the complex interaction between genetic and environmental factors. For soldiers exposed to combat, the risk of developing this disorder is twofold and diagnosis is often late, when much sequela has set in. To be able to identify and diagnose in advance those at "risk" of developing post-traumatic stress disorder, would greatly taper the gap between late sequelae and treatment. Therefore, this study sought to determine whether the transcriptome can be used to track the development of post-traumatic stress disorder in this unique and susceptible cohort of individuals. Gene expression levels in peripheral blood samples from 85 Canadian infantry soldiers (n = 58 participants negative for symptoms of post-traumatic stress disorder and n = 27 participants with symptoms of post-traumatic stress disorder) following return from deployment to Afghanistan were determined using RNA sequencing technology. Count-based gene expression quantification, normalization and differential analysis (with thorough correction for confounders) revealed genes associated to PTSD; LRP8 and GOLM1 These preliminary results provide a proof-of-principle for the diagnostic utility of blood-based gene expression profiles for tracking symptoms of post-traumatic stress disorder in soldiers returning from tour. It is also the first to report transcriptome-wide expression profiles alongside a post-traumatic symptom checklist.
| S-EPMC6385974 | biostudies-literature
Project description:The molecular factors involved in the development of Post-traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network-based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD. We used microarrays to characterize both prognostic and diagnostic molecular signatures associated to PTSD risk and PTSD status compared to control subjects. Peripheral blood leukocytes gene expression was subject to transcriptional analysis for 48 service members both prior-to and following deployment to conflict zones. Half of the subjects returned with Post-traumatic Stress Disorder (PTSD), while the other half did not.
2015-02-27 | E-GEOD-63878 | biostudies-arrayexpress
Project description:The molecular factors involved in the development of Post-Traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD. We used RNA-Sequencing gene expression to characterize both prognostic and diagnostic molecular signatures associated to PTSD risk and PTSD status compared to control subjects. Peripheral blood luekocytes gene expression was subject to transcriptional analysis for 94 service members both prior-to and following-deployment to conflict zones. Half of the subjects returned with Post-traumatic stress disorder (PTSD), while the other half did not.
2015-02-27 | E-GEOD-64813 | biostudies-arrayexpress
Project description:The molecular factors involved in the development of Post-traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network-based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD. We used microarrays to characterize both prognostic and diagnostic molecular signatures associated to PTSD risk and PTSD status compared to control subjects.
2015-02-27 | GSE63878 | GEO
Project description:The molecular factors involved in the development of Post-Traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD. We used RNA-Sequencing gene expression to characterize both prognostic and diagnostic molecular signatures associated to PTSD risk and PTSD status compared to control subjects.
2015-02-27 | GSE64813 | GEO
Project description:Growth mixture model studies have observed substantial differences in the longitudinal patterns of posttraumatic stress symptom (PTSS) trajectories. This variability could represent chance iterations of some prototypical trajectories or measurable variability induced by some aspect of the source population or traumatic event experience. Testing the latter, the authors analyzed a nationally representative sample of U.S. Reserve and National Guard members to identify the influence of civilian versus deployment trauma on the number of PTSS trajectories, the nature of these trajectories, and the proportion of respondents in each trajectory.Data were collected from 2010 to 2013 and latent class growth analysis was used to identify different patterns of PTSS in persons exposed to both a civilian and a deployment trauma and to test whether respondents' exposure to civilian trauma developed similar or distinct patterns of response compared to respondents exposed to deployment trauma.PTSS were found to follow 3 trajectories, with respondents predominantly clustered in the lowest symptom trajectory for both trauma types. Covariates associated with each trajectory were similar between the 2 traumas, except number of civilian-related traumatic events; specifically, a higher number of civilian traumatic events was associated with membership in the borderline-stable, compared to low-consistent, trajectory, for civilian traumas and associated with the preexisting chronic trajectory for military traumas.Holding the source population constant, PTSS trajectory models were similar for civilian and deployment-related trauma, suggesting that irrespective of traumatic event experienced there might be some universal trajectory patterns. Thus, the differences in source populations may have induced the heterogeneity observed among prior PTSS trajectory studies. (PsycINFO Database Record
| S-EPMC5161718 | biostudies-other
Project description:Traumatic brain injury (TBI) contributes to the increased rates of suicide and post-traumatic stress disorder in military personnel and veterans, and it is also associated with the risk for neurodegenerative and psychiatric disorders. A cross-phenotype high-resolution polygenic risk score (PRS) analysis of persistent post-concussive symptoms (PCS) was conducted in 845 U.S. Army soldiers who sustained TBI during their deployment. We used a prospective longitudinal survey of three brigade combat teams to assess deployment-acquired TBI and persistent physical, cognitive, and emotional PCS. PRS was derived from summary statistics of large genome-wide association studies of Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, and major depressive disorder (MDD); and for years of schooling, college completion, childhood intelligence, infant head circumference (IHC), and adult intracranial volume. Although our study had more than 95% of statistical power to detect moderate-to-large effect sizes, no association was observed with neurodegenerative and psychiatric disorders, suggesting that persistent PCS does not share genetic components with these traits to a moderate-to-large degree. We observed a significant finding: subjects with high IHC PRS recovered better from cognitive/emotional persistent PCS than the other individuals (R2?=?1.11%; p?=?3.37?×?10-3). Enrichment analysis identified two significant Gene Ontology (GO) terms related to this result: GO:0050839?Cell adhesion molecule binding (p?=?8.9?×?10-6) and GO:0050905?Neuromuscular process (p?=?9.8?×?10-5). In summary, our study indicated that the genetic predisposition to persistent PCS after TBI does not have substantial overlap with neurodegenerative and psychiatric diseases, but mechanisms related to early brain growth may be involved.
| S-EPMC5314978 | biostudies-literature
Project description:Introduction:Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are two of the signature injuries in military service members who have been exposed to explosive blasts during deployments to Iraq and Afghanistan. Acute stress disorder (ASD), which occurs within 2-30 d after trauma exposure, is a more immediate psychological reaction predictive of the later development of PTSD. Most previous studies have evaluated service members after their return from deployment, which is often months or years after the initial blast exposure. The current study is the first large study to collect psychological and neuropsychological data from active duty service members within a few days after blast exposure. Materials and Methods:Recruitment for blast-injured TBI patients occurred at the Air Force Theater Hospital, 332nd Air Expeditionary Wing, Joint Base Balad, Iraq. Patients were referred from across the combat theater and evaluated as part of routine clinical assessment of psychiatric and neuropsychological symptoms after exposure to an explosive blast. Four measures of neuropsychological functioning were used: the Military Acute Concussion Evaluation (MACE); the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); the Headminder Cognitive Stability Index (CSI); and the Automated Neuropsychological Assessment Metrics, Version 4.0 (ANAM4). Three measures of combat exposure and psychological functioning were used: the Combat Experiences Scale (CES); the PTSD Checklist-Military Version (PCL-M); and the Acute Stress Disorder Scale (ASDS). Assessments were completed by a deployed clinical psychologist, clinical social worker, or mental health technician. Results:A total of 894 patients were evaluated. Data from 93 patients were removed from the data set for analysis because they experienced a head injury due to an event that was not an explosive blast (n = 84) or they were only assessed for psychiatric symptoms (n = 9). This resulted in a total of 801 blast-exposed patients for data analysis. Because data were collected in-theater for the initial purpose of clinical evaluation, sample size varied widely between measures, from 565 patients who completed the MACE to 154 who completed the CES. Bivariate correlations revealed that the majority of psychological measures were significantly correlated with each other (ps ? 0.01), neuropsychological measures were correlated with each other (ps ? 0.05), and psychological and neuropsychological measures were also correlated with each other (ps ? 0.05). Conclusions:This paper provides one of the first descriptions of psychological and neuropsychological functioning (and their inter-correlation) within days after blast exposure in a large sample of military personnel. Furthermore, this report describes the methodology used to gather data for the acute assessment of TBI, PTSD, and ASD after exposure to an explosive blast in the combat theater. Future analyses will examine the common and unique symptoms of TBI and PTSD, which will be instrumental in developing new assessment approaches and intervention strategies.
| S-EPMC7263835 | biostudies-literature
Project description:Background: Soldiers' perception of leadership during military deployment has gained research attention as a potentially modifiable factor to buffer against the development of postdeployment post-traumatic stress disorder (PTSD). Within nonmilitary research, the organizational justice (OJ) framework, i.e. distributive justice, procedural justice (PJ) and interactional justice (IJ), has been found to relate to mental health outcomes. Aspects of OJ may, therefore, be protective against PTSD. Objectives: We examined the prospective relationship between aspects of OJ, namely the perceptions of PJ and IJ by subordinate soldiers without leadership obligations in relationship to immediate superiors and PTSD. Method: Participants were soldiers (n = 245) deployed to Helmand Province in Afghanistan in 2009. Logistic regression procedures were used. The primary analysis measured PTSD cases using the Structured Clinical Interview for DSM-IV-TR Axis-I Disorder (SCID) 2½ years after homecoming. PJ/IJ was measured during deployment with a 6-item composite measure ranging from 0 to 12. Supplementary primary analyses were performed with PJ/IJ measured before and immediately after deployment. A secondary PJ/IJ analysis also tested against four postdeployment measures with the Post-Traumatic Stress Disorder Checklist Civilian (PCL-C) dichotomized at screening symptom levels. Results: Higher levels of perceived PJ/IJ for soldiers without leadership obligations during deployment had a prospective relation (OR = 0.86, 95% CI = 0.75-0.98) with PTSD on the SCID 2½ years after homecoming after adjustment for factors including predeployment PTSD symptoms, trauma and combat exposure, and state affectivity. Similar results were found by measuring PJ/IJ before (OR = 0.83, 95% CI = 0.71-0.95) but not immediately after homecoming (OR = 0.97, 95% CI = 0.85-1.11). A relationship with PTSD symptoms at the screening level at the four measurements of PCL-C was found, but only when predeployment PTSD symptoms were not controlled for. Conclusions: These results suggest that PJ/IJ exercised by superiors in relation to military deployments may protect subordinate soldiers against the development of postdeployment PTSD.
| S-EPMC5912440 | biostudies-literature