Identification of Biomarkers for Stress Vulnerability and Resilience
Abstract
The goal of this project is to develop biomarkers for predicting stress vulnerability or stress resilience in young healthy subjects. Predicting how individuals might respond to a major trauma or to a severe and sustained period of stress is important in recognizing and preventing the consequences of severe stressors. These adverse consequences include disorders, such as Post-Traumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD) and other mood and anxiety disorders. With ONR funding, we have initiated a project using a combination of genetic markers, and neuroendocrine and affective responses to a stress challenge to predict responsiveness to highly stressful ~real life~ events. Subjects are followed-up in a naturalistic setting expected to trigger sustained stress. The study involves two groups of subjects- Medical Interns as they progress through their internship year, and college freshmen as they progress through their freshman year. The first 2 cohorts have helped us generate an algorithm that predicts the emergence of both clinical anxiety and clinical depression during stress. The current proposal aims to replicate and extend the above work. It adds to the design a pre-screening based on genotyping the subjects prior to the start of the stressful period, calculating a ~polygenic risk score~ (PRS) and selecting subjects who are genetically highly vulnerable or genetically highly resilient. We will ask whether the combination of this genetic information with the other biomarkers we have identified has added predictive power These human studies will be coupled to studies in our genetic rat lines that model differences in temperamental tendencies, with one line being akin to humans prone to ~internalizing disorders~ and the other to humans prone to ~externalizing disorders~. The animal studies will be used to a) validate the data generated in humans; b) identify novel gene targets; and c) lay the groundwork for additional types of analysis. This combination of human and animal studies should help us arrive at a strategy for predicting vulnerability or resilience to sustained life stress in a population of young, healthy individuals. APPROVED FOR PUBLIC RELEASE.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 25, 2019
- Source ID
- N000141912149
Entities
People
- Huda Akil
Organizations
- Board of Regents of the University of Michigan
- Office of Naval Research
- United States Navy