Extracellular vesicles as biomarkers of trauma exposure and PTSD risk

NIH RePORTER · NIH · R01 · $51,045 · view on reporter.nih.gov ↗

Abstract

ABSTRACT Childhood trauma, particularly interpersonal violence (IPV) exposure, is widespread and associated with long- term negative health outcomes, including increased risk for neuropsychiatric disorders such as posttraumatic stress disorder (PTSD) and mood disorders. Physiological responses to stress, if chronic or severe enough and especially those occurring during vulnerable life periods such as adolescence, can promote lasting systemic changes and may contribute to health inequities seen in vulnerable populations. Exposure to trauma prior to age 14 has differential effects compared to exposure later in adolescence, but little is known about the biological mechanisms that underlie differential effects of trauma timing. A key biological marker that holds potential in human subject studies is the extracellular vesicle (EV). Changes in EV size and protein content are responsive to stress, can be easily assayed, and are predictive of functionality and tissue specificity important for health and disease. We recently identified a unique protein signature in blood plasma from an unbiased EV proteomic analysis in Black women who had experienced IPV during adolescence (14-18 years of age). This diversity supplement will examine dynamic changes in EV characteristics associated with fear conditioning and relate those changes to the developmental timing of IPV exposure (i.e. childhood vs. adolescence) utilizing a longitudinal birth cohort of Black Americans who grew up in an under-resourced urban environment. We will determine whether dynamic changes in EV characteristics quantified before and after fear conditioning differ based on developmental timing of interpersonal violence by comparing participants who experienced IPV before age 14, between ages 14-18, or did not experience IPV trauma. We will also examine whether individual differences in EV characteristics quantified before and after fear conditioning correlate with individual differences in fear-potentiated startle. This project will contribute to understanding EV’s potential as biomarkers for systemic impacts of interpersonal violence experienced during vulnerable time periods and provide vital information to elucidate potential novel targets for identification of and early intervention for individuals at risk of stress-related neuropsychiatric disorders.

Key facts

NIH application ID
11013708
Project number
3R01MH129495-02S1
Recipient
UNIVERSITY OF COLORADO DENVER
Principal Investigator
Tracy L Bale
Activity code
R01
Funding institute
NIH
Fiscal year
2024
Award amount
$51,045
Award type
3
Project period
2024-03-01 → 2027-06-30