Comorbid post-traumatic stress disorder and major depressive disorder (PTSD+MDD) is the most common pathological response to trauma and represents a major public health burden. Unfortunately, knowledge regarding the neurobiological mechanisms underlying this comorbidity is extremely limited. Without such an understanding, treatment outcomes for this common constellation will likely remain poor.
The overall research objective of this project is to use an experimental medicine conceptualization of serial ketamine infusions as a probe to:
- Characterize neurobiological factors underpinning PTSD+MDD
- Demonstrate that modulation of corticolimbic functional connectivity generates clinical improvement
- Validate a coherent model of PTSD+MDD to inform future research, treatment, and conceptualizations
The project's central hypothesis is that corticolimbic dysconnectivity is associated with clinical symptoms, rumination, and cognitive dysfunction in PTSD+MDD and that ketamine infusions correct dysconnectivity thereby improving in clinical symptoms, rumination, and cognition. The specific aims of this research are:
- To examine how baseline PTSD+MDD clinical presentation, cognitive function and neurocircuitry predicts clinical response to ketamine infusions
- To examine the association of changes in corticolimbic circuitry with changes in clinical symptoms and cogntion following either ketamine or saline infusions
An exploratory aim of this study is to examine cognition, rumination, and neurocircuitry in a larger cohort of trauma exposed subjects as well as healthy controls.