Mitochondrial Dysfunction in PTSD and Comorbid Conditions
Abstract
The biological causes of posttraumatic stress disorder (PTSD) are poorly understood, and this hampers attempts at developing maximally effective treatments. This is especially urgent, as only 30% of individuals with PTSD currently fully respond to approved medications. This project will investigate a new promising candidate mechanism, brain mitochondrial dysfunction, involved in the biology of PTSD (and commonly co-occurring illnesses, depression and traumatic brain injury TBI). Although considerable evidence supports the concept of mitochondrial dysfunction in PTSD, this have never been investigated in brain mitochondria, which are the most likely to be relevant to PTSD. The current approach, based on recently developed and easy-to-obtain blood tests, will finally enable those investigations. The Fiscal Year 2021 Traumatic Brain Injury and Psychological Health Research Program Investigator-Initiated Research Award Focus Area(s) to be addressed by the proposed research include: (1) addressing knowledge gaps in foundational science and etiology of combat trauma-associated psychological illness (PTSD alone or comorbid with major depression or TBI); (2) understanding of pre-exposure risk, and biological factors contributing to an individual’s response, recovery, and long-term outcomes following combat trauma-associated psychological illness; (3) identification and validation of biomarkers or other objective markers for diagnosis, prognosis, or monitoring of psychological health conditions/brain injuries; (4) identifying biological abnormalities that can be targets for novel treatments, and interventions and personalized medicine approaches that can be tailored to the biological and endophenotypic elements present; (5) novel therapeutic candidates based on evolving changes of pathophysiology and/or theoretical mechanisms of TBI and psychological health. Identification of brain mitochondrial dysfunction in PTSD and co-occurring illnesses will enable enhanced risk prediction, more biologically informed diagnoses and, most importantly, the development of new, effective and more personalized medication treatments specifically aimed at correcting this mitochondrial dysfunction. This progress will benefit traumatized active-duty Soldiers and combat Veterans as well as civilians with PTSD. If proven to be of value, this blood test could be commercially scaled rapidly, to quickly benefit patients and researchers. Since the assay technology is already available, person-related outcomes could be forthcoming within a short time frame. Specifically, identifying brain mitochondrial dysfunction in patients with PTSD (alone or in conjunction with depression or TBI) along the lines proposed in this project’s aims could allow early screening for vulnerability markers for developing PTSD, could aid in predicting the course of illness in PTSD, could help monitor the efficacy of treatment in ameliorating certain underlying biological problems in PTSD, and, perhaps most importantly, could identify biological abnormalities in PTSD that could be addressed by new classes of medication. As we discuss in this proposal, there are already pharmaceutical agents that are known to improve mitochondrial function and that could be rapidly tested and repurposed for treatment of PTSD. In particular, this could lead to more personalized treatment of patients with PTSD, since only those with evidence of brain mitochondrial dysfunction would be suitable candidates for this type of treatment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210704
Entities
People
- Synthia H Mellon
Organizations
- United States Army
- University of California, San Francisco