Aryl Hydrocarbon Receptor Activation in PTSD and Comorbid Psychological Disorders
Abstract
Post-traumatic Stress Disorder (PTSD) is common amongst combat exposed military personnel, but its pathophysiology is poorly understood. Current approved treatments, targeting the serotonergic system, fail to fully reduce the burden of this disease and do not account for dysfunction in other mechanistic pathways including immune dysregulation and inflammation. In this proposal, we focus on an understudied signaling pathway, the Aryl Hydrocarbon Receptor (AhR) pathway, in the pathophysiology of PTSD and associated psychological conditions after combat exposure. This pathway has been shown to modulate a wide variety of physiological processes including immune function and changes in the activation of this pathway have been identified in diseases with an inflammatory component. Furthermore, studies in MDD have demonstrated that ligands for these receptors are altered, specifically demonstrating that those with pro-inflammatory activity (kynurenine) are increased and those with an anti-inflammatory activity (Indoles) are reduced. In this proposal, we investigate not only overall AhR signaling, but also study known AhR ligands which have been implicated in psychiatric disease and their role in the development of PTSD. Plasma samples for assay have recently been obtained and we have been able to demonstrate the ability of our cell based assay to reliably detect kynurenine metabolites of tryptophan. We are now optimizing the assay to detect AhR ligands in the plasma. Additionally, targeted metabolomics for kynurenine and indole metabolites of tryptophan will be completed shortly and will allow us to determine the physiological concentrations of these metabolites.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1216549
Entities
People
- Gwyneth Wu
- Owen M. Wolkowitz
- Ryan Rampersaud
- Sindy Mellon
Organizations
- University of California, San Francisco