The Role of Medial Amygdala Circuits in Mediating the Effects of Diet on Post-Traumatic Behavioral and Metabolic Complications
Abstract
Most U.S. adults (68%-89%) have experienced a severe traumatic event, and this proportion is even higher in military and Veteran populations (99%) due to exposure to combat and related situations. Trauma exposure increases the risk of a range of mental health disorders, from heightened fear and increased arousal characteristic of post-traumatic stress disorder (PTSD), to anxiety, eating disorders, and sleep disturbances. Recent studies report that the prevalence of PTSD in U.S. military Veterans is as high as 31%, while other mental health disorders affect over a third of military personnel. In parallel, trauma increases the risk of metabolic diseases such as obesity, diabetes, and cardiovascular disease. In the U.S., one in nine people have diabetes and 84 million people are pre-diabetic, but incidence is even higher in at-risk groups, such as Veterans. One in four veterans has diabetes, and there is a strong association between PTSD and metabolic diseases such as diabetes. Mental health disorders and metabolic diseases place enormous burdens on the affected individual, their family, and the larger community. Mental health disorders and metabolic diseases after trauma are difficult to treat. Existing treatments for PTSD and additional mental health disorders after trauma have limited efficacy. There are few methods to prevent the psychological complications of trauma. Similarly, preventing and treating metabolic disease is difficult. A healthy diet and exercise regimen that reduces weight decreases the risk of diabetes, but these changes are difficult to maintain over time. So, a broader range of and better therapies to lower risks and to treat mental health and metabolic disorders after trauma are clearly needed. The studies proposed here will form a foundation for new therapies to prevent and treat the complications of psychological trauma. Despite the known associations between intense stress, mental health disorders, and metabolic disease, systematic studies examining the mechanisms that link these factors are missing. The goal of our studies is to understand the interactions between traumatic stressors and nutrition in the development of psychological disorders and metabolic disease. To do so, we will dissect the key roles of a crucial brain region called the medial amygdala in integrating information about trauma and high-fat diet on behavior and metabolic health. Our pilot studies already show that intense stress combined with over-nutrition result in anxiety-like behavior, abnormal feeding, and increased blood glucose. Using new and improved imaging techniques, we can see that medial amygdala neurons are switched on by intense stress in real time, as well as by over-eating. Additionally, using improved technologies, we can switch on or switch off the neurons in the medial amygdala and so rapidly change activity, feeding, and blood glucose, showing this region plays key roles in regulating behavior and glucose control. Finally, our novel approach allows us to identify the crucial cell types, their location, and the genetic mechanisms that are critical for interactions between trauma and nutrition. In this proposal, we will be using our novel combination of innovative techniques to understand how trauma and nutrition interact to modulate neural activity, function, and gene expression in the development of mental health disorders and metabolic disease. These studies will provide the foundation for understanding how trauma and nutritional environment interact to increase vulnerability to mental health disorders and metabolic diseases. By identifying the mechanisms contributing to behavioral and metabolic abnormalities after trauma and how they are disrupted by poor diet, we will be able to identify at-risk individuals and target interventions such as behavioral modifications, diet, or drugs to prevent or treat the devastating consequences of trauma. The information from this project is a critical first step towar
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310245
Entities
People
- Abha Rajbhandari
Organizations
- Icahn School of Medicine at Mount Sinai
- United States Army