Key Dimensions of PTSD and ED

Key Dimensions of Post-traumatic Stress Disorder (PTSD) and Endothelial Dysfunction (ED)

This study will test whether endothelial dysfunction could be the early subclinical mechanism by which posttraumatic stress disorder (PTSD) increases cardiovascular disease (CVD) risk, and whether posttraumatic fear-a key component of PTSD-or another PTSD dimension could be the target to offset that risk. The results of this study may help trauma-exposed individuals who are at risk of having CVD events.

Study Overview

• Status: Completed
• Conditions: PTSD; Trauma; Endothelial Dysfunction
• Intervention / Treatment: Behavioral: Psychophysiological fear conditioning and extinction task; Behavioral: Eyetracking task

Detailed Description

Posttraumatic stress disorder (PTSD) increases risk of incident cardiovascular disease (CVD) by 25-50%. Most individuals (50-90%) experience a traumatic event in their lifetime, and PTSD is the fifth most common psychiatric disorder. Experts have now called for increased CVD surveillance after trauma and for PTSD treatment trials powered to reduce CVD risk. However, both CVD risk and PTSD are complex phenomena that likely interact in nuanced ways. This study will determine which PTSD dimension(s) contribute to endothelial dysfunction, one of the earliest modifiable precursors to CVD. The investigators will examine cross-sectional and longitudinal associations of PTSD and its underlying dimensions with functional and, secondarily, cellular measures of endothelial dysfunction (FMD and circulating endothelial cell-derived microparticles, respectively) in a community-dwelling sample of CVD-free adult men and women with a history of trauma (50% with current PTSD).

• Study Type: Observational
• Enrollment (Actual): 168

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Trauma-exposed adults without a history of cardiovascular disease recruited from the community

Description

Inclusion Criteria:

• Aged 18+ years
• History of exposure to a psychological trauma (e.g., natural disaster, physical assault)
• Fluent in English
• Willing to and capable of providing informed consent

Additional Inclusion Criteria for the PTSD Group

• Diagnosed with current PTSD (duration of at least 1 month) using the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual 5th Edition (DSM-5) (CAPS-5) at the diagnostic interview assessment

Exclusion Criteria:

• History of CVD (i.e., diagnosis of myocardial infarction, unstable angina, heart failure, peripheral artery disease, or stroke)
• Deemed unable to comply with the protocol (either self-selected or by indicating during screening that could not complete all requested tasks)
• Current bipolar disorder or psychotic disorder
• Mild or more severe cognitive impairment [Mini-Mental State Exam (MMSE)3 score ≤18]
• Current moderate or severe substance use disorder
• Acute, unstable, or severe medical disorder or pregnancy
• Deemed to need immediate psychiatric intervention (e.g., active suicidality)
• Use of antipsychotic, mood stabilizer, antidepressant, or stimulant medication in the past 4 weeks
• Daily benzodiazepine use in the past 2 weeks

Additional Exclusion Criteria for the Trauma-Exposed Matched Control Group

• Current or past diagnosis of any DSM-5 psychiatric disorder
• CAPS-5 total score ≥25

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Trauma exposed without PTSD; Individuals with a history of trauma exposure who do not have current PTSD	Behavioral: Psychophysiological fear conditioning and extinction task; Behavioral task to assess psychophysiological measures of fear; Behavioral: Eyetracking task; Behavioral task to assess dysphoria-relevant attention allocation
Trauma exposed with PTSD; Individuals with a history of trauma exposure and a current diagnosis of PTSD	Behavioral: Psychophysiological fear conditioning and extinction task; Behavioral task to assess psychophysiological measures of fear; Behavioral: Eyetracking task; Behavioral task to assess dysphoria-relevant attention allocation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow-mediated Dilation of the Brachial Artery (FMD) %	FMD is the percent difference in diameter of the brachial artery, before and after occlusion. Impaired endothelial function occurs when blood vessels are unable to dilate fully in response to nitric oxide synthesis and release, which is manifested as impaired endothelium-dependent vasodilation (i.e., lower FMD). Lower FMD has been associated with the degree of coronary atherosclerosis and predicts CVD events.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating Endothelial Cell-derived Microparticles (EMPs) Expressing CD62E	EMPs expressing CD62E (i.e., endothelial cell activation) and CD31 (i.e., endothelial cell apoptosis) will be measured. Assessments of circulating EMPs will be measured using flow cytometry, and total flow cytometry counts will be converted to the number of EMPs per uL of blood. Higher concentrations of EMPs expressing CD62E and CD31 indicate greater endothelial dysfunction.	Baseline
Circulating Endothelial Cell-derived Microparticles (EMPs) Expressing CD31	EMPs expressing CD62E (i.e., endothelial cell activation) and CD31 (i.e., endothelial cell apoptosis) will be measured. Assessments of circulating EMPs will be measured using flow cytometry, and total flow cytometry counts will be converted to the number of EMPs per uL of blood. Higher concentrations of EMPs expressing CD62E and CD31 indicate greater endothelial dysfunction.	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fear Load Based on Fear-potentiated Startle During Early Extinction	Fear-potentiated startle (FPS) to the danger cue (CS+) during early extinction as part of a fear acquisition and extinction paradigm; this measure reflects expression of conditioned fear during early extinction. FPS is measured through corrugator and orbicularis electromyography (EMG). Startle magnitude is assessed as the peak amplitude (in microVolts) of EMG contraction 20-200ms following the startle probe. A difference score for FPS is calculated by subtracting the startle magnitude to the noise alone probe from the startle magnitude to the CS to account for individual differences in startle magnitude and habituation. Higher values of this FPS difference score indicate greater fear load (i.e., greater overexpression of conditioned fear to a now safe signal during early extinction), which has been associated with PTSD.	Baseline
Averaged Total Dwell Time for Happy Faces	Averaged total dwell time of the happy faces Area of Interest (AOI) across 60 face matrices; reflects continuous gaze allocation to happy stimuli	Baseline
Averaged Total Dwell Time for Sad Faces	Averaged total dwell time of the sad faces Area of Interest (AOI) across 60 face matrices; reflects continuous gaze allocation to sad stimuli	Baseline

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Jennifer A Sumner, PhD, University of California, Los Angeles

Publications and helpful links

General Publications

• Cleveland S, Reed K, Thomas JL, Ajijola OA, Ebrahimi R, Hsiai T, Lazarov A, Montoya AK, Neria Y, Shimbo D, Wolitzky-Taylor K, Sumner JA. Key dimensions of post-traumatic stress disorder and endothelial dysfunction: a protocol for a mechanism-focused cohort study. BMJ Open. 2021 May 5;11(5):e043060. doi: 10.1136/bmjopen-2020-043060.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2019
• Primary Completion (Actual): June 30, 2025
• Study Completion (Actual): June 30, 2025

Study Registration Dates

• First Submitted: December 7, 2018
• First Submitted That Met QC Criteria: December 14, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: PTSD; Trauma; Endothelial Dysfunction
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Wounds and Injuries; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: AAAR8563; R01HL139614 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No