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Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development.

ABSTRACT: Post-traumatic stress disorder (PTSD) is a condition of stress reactivity, whose clinical manifestations are evident when patients are triggered following exposure to a traumatic event. While baseline differences in gene expression of glucocorticoid signaling and inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) have been associated with PTSD, these alterations do not fully recapitulate the molecular response to physiological triggers, such as stress hormones. Therefore, it is critical to develop new techniques that will capture the dynamic transcriptional response associated with stress-activated conditions relative to baseline conditions. To achieve this goal, cultured PBMCs from combat-exposed veterans with PTSD(+) (n?=?10) and without PTSD(-) (n?=?10) were incubated with increasing concentrations (vehicle, 2.5?nM, 5?nM, 50?nM) of dexamethasone (DEX). Across diagnosis and dosage, several genes and gene networks were reliable markers of glucocorticoid stimulation (FDR?

SUBMITTER: Breen MS

PROVIDER: S-EPMC6704073 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development.

Breen Michael S MS Bierer Linda M LM Daskalakis Nikolaos P NP Bader Heather N HN Makotkine Iouri I Chattopadhyay Mitali M Xu Changxin C Buxbaum Grice Ariela A Tocheva Anna S AS Flory Janine D JD Buxbaum Joseph D JD Meaney Michael J MJ Brennand Kristen K Yehuda Rachel R

Translational psychiatry 20190821 1

Post-traumatic stress disorder (PTSD) is a condition of stress reactivity, whose clinical manifestations are evident when patients are triggered following exposure to a traumatic event. While baseline differences in gene expression of glucocorticoid signaling and inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) have been associated with PTSD, these alterations do not fully recapitulate the molecular response to physiological triggers, such as stress hormones. Therefore, it is ...[more]

PMID: 31434874

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Project description:BackgroundRecent years have shown an increased application of prospective trajectory-oriented approaches to posttraumatic stress disorder (PTSD). Although women are generally considered at increased PTSD risk, sex and gender differences in PTSD symptom trajectories have not yet been extensively studied.ObjectiveTo perform an in-depth investigation of differences in PTSD symptom trajectories across one-year post-trauma between men and women, by interpreting the general trends of trajectories observed in sex-disaggregated samples, and comparing within-trajectory symptom course and prevalence rates.MethodWe included N = 554 participants (62.5% men, 37.5% women) from a multi-centre prospective cohort of emergency department patients with suspected severe injury. PTSD symptom severity was assessed at 1, 3, 6, and 12 months post-trauma, using the Clinician-Administered PTSD Scale for DSM-IV. Latent growth mixture modelling on longitudinal PTSD symptoms was performed within the sex-disaggregated whole samples. Bayesian modelling with informative priors was applied for reliable model estimation, considering the imbalanced prevalence of the expected latent trajectories.ResultsIn terms of general trends, the same trajectories were observed for men and women, i.e. resilient, recovery, chronic symptoms and delayed onset. Within-trajectory symptom courses were largely comparable, but resilient women had higher symptoms than resilient men. Sex differences in prevalence rates were observed for the recovery (higher in women) and delayed onset (higher in men) trajectories. Model fit for the sex-disaggregated samples was better than for the whole sample, indicating preferred application of sex-disaggregation. Analyses within the whole sample led to biased estimates of overall and sex-specific trajectory prevalence rates.ConclusionsSex-disaggregated trajectory analyses revealed limited sex differences in PTSD symptom trajectories within one-year post-trauma in terms of general trends, courses and prevalence rates. The observed biased trajectory prevalence rates in the whole sample emphasize the necessity to apply appropriate statistical techniques when conducting sex-sensitive research.

Dataset Information

Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development.

Publications

Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development.

Similar Datasets

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