Key dimensions of post-traumatic stress disorder and endothelial dysfunction: a protocol for a mechanism-focused cohort study

Abstract

IntroductionBoth trauma exposure and post-traumatic stress disorder (PTSD) are associated with increased risk of cardiovascular disease (CVD), the leading cause of death in the USA. Endothelial dysfunction, a modifiable, early marker of CVD risk, may represent a physiological mechanism underlying this association. This mechanism-focused cohort study aims to investigate the relationship between PTSD (both in terms of diagnosis and underlying symptom dimensions) and endothelial dysfunction in a diverse, community-based sample of adult men and women.Methods and analysisUsing a cohort design, 160 trauma-exposed participants without a history of CVD are designated to the PTSD group (n=80) or trauma-exposed matched control group (n=80) after a baseline diagnostic interview assessment. Participants in the PTSD group have a current (past month) diagnosis of PTSD, whereas those in the control group have a history of trauma but no current or past psychiatric diagnoses. Endothelial dysfunction is assessed via flow-mediated vasodilation of the brachial artery and circulating levels of endothelial cell-derived microparticles. Two higher order symptom dimensions of PTSD—fear and dysphoria—are measured objectively with a fear conditioning paradigm and attention allocation task, respectively. Autonomic imbalance, inflammation, and oxidative stress are additionally assessed and will be examined as potential pathway variables linking PTSD and its dimensions with endothelial dysfunction. Participants are invited to return for a 2-year follow-up visit to reassess PTSD and its dimensions and endothelial dysfunction in order to investigate longitudinal associations.Ethics and disseminationThis study is conducted in compliance with the Helsinki Declaration and University of California, Los Angeles Institutional Review Board. The results of this study will be disseminated via articles in peer-reviewed journals and presentations at academic conferences and to community partners.Trial registration numberNCT03778307; pre-results.

Posttraumatic stress disorder in patients with cardiovascular diseases

“…Недостатня вазодилатація в умовах підвищеного серцево-судинного навантаження призводить до збільшення жорсткості судинної стінки, запальної реакції та активації протромботичних процесів [79]. Два дослідження, які оцінювали зв'язок ПТСР з ЕД, виявили, що в пацієнтів з ПТСР спостерігалося клінічно значуще зниження потокозалежної вазодилататорної відповіді плечової артерії, за даними тесту з реактивною гіперемією [16,30]. ЕД разом із гіперкоагуляційним станом може сприяти гострим атеротромботичним серцево-судинним подіям [5].…”

PTSD as an Endothelial Disease: Insights From COVID-19

“…Novel studies reported premature endothelial senescence in veterans and non-veterans with PTSD, indicating that BBB disruption likely plays a pivotal role in this disorder (Boscarino, 2008;Grenon et al, 2016;Thurston et al, 2018). Others have found that war veterans with PTSD, like older individuals, present with defective mitochondria, telomeres, furin/plasmin, and BDNF, connecting cerebral EC senescence with dysfunctional subcellular structures (Levin et al, 1997;Doughan et al, 2008;Gray and Ellis, 2008;Fleegal-DeMotta et al, 2009;Khoury et al, 2012;Grenon et al, 2016;Aksu et al, 2018;Connolly et al, 2018; Stein et al, 2018;Miranda et al, 2019;Seligowski et al, 2021;Cleveland et al, 2021).…”

Cerebral Blood Flow in Predator Stress-Resilient and -Susceptible Rats and Mechanisms of Resilience

“…Thus, disturbed regulation of CBF can play an important role in the high risk of both cardiovascular and mental disorders following severe stress [ 7 ]. Accordingly, special attention should be paid to endothelial dysfunction [ 13 , 14 , 15 ] as a factor affecting CBF after severe stress.…”