A Novel Approach to Predicting Resilience to Post-Traumatic Stress Disorder
Abstract
PTSD is an anxiety disorder that may develop following exposure to strongly traumatic event(s). These patients often experience exaggerated fear and anxiety, flashback memories, social withdrawal, etc. Unfortunately, there are limited options in managing or effectively treating PTSD symptoms. Therefore, there is an urgent need to understand the underlying genetic and neural causes of PTSD. Many war fighters returning from combat often suffered from PTSD. Emerging evidence suggest that there is a strong correlational differences between changes in heart physiology such as heart rate variability (HRV) in PTSD and non-PTSD groups. However, it is no clear whether reported HRV changes in PTSD veterans reflected the secondary results from combat stress and PTSD progression, or the individual predispositions that preceded onset of PTSD. Due to many practical constraints, little information is available regarding realtime changes in these vital signs during or immediately after combat or traumatic events in humans. Moreover, it is not clear how the central nerve system, especially the DA neuron circuit, regulates heart rates (HR) and HRV. In this application, we postulate three novel hypotheses: 1) NMDA receptors in DA neurons are crucial for generating robust phasic firing and safety-learning signals in the VTA in response to stressful environments and events. 2) Abnormal VTA DA neuron activities lead to abnormal HR and HRV. 3) Restoration of DA neuron phasic activation (via optogenetic manipulation) can reduce PTSD-like anxiety overgeneralization and rescue HRV abnormality in the DA-NRl-KO mice. Over the next three years we will combine in vivo electrophysiological techniques with dopamine neuron-specific knockout and optogenetic method to study and manipulate DA neuron firing properties and HR and HRV. Our study should shed fundamental insights into how dopaminergic neurons engage in regulating anxiety behaviors. More importantly, it will reveal a novel approach to predict PTSD resilience among war fighters as well as to treat PTSD, thereby leading to broad long-term impact on army operation, military family, and society.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 07, 2018
- Source ID
- W911NF1710534
Entities
People
- Joe Tsien
Organizations
- Army Contracting Command
- Medical College of Georgia
- United States Army