Evidence for Distinct Neuromolecular Biotypes of Posttraumatic Stress Disorder: Predicting Resting-State Network Connectivity Dysfunction

Meghan Pierce, Ph.D.

VA Boston Healthcare System
Evidence for Distinct Neuromolecular Biotypes of Posttraumatic Stress Disorder: Predicting Resting-State Network Connectivity Dysfunction

Scientific Abstract

 

Background: Posttraumatic stress disorder (PTSD) is a heterogeneous condition in its symptom presentation, long-term outcomes, and underlying neurobiology. This heterogeneity may be related to underlying biotypes of PTSD. The present study will explore the existence of neuromolecular biotypes of PTSD by integrating blood- and neuroimaging-based modalities.

Methods: Participants were 99 male Veterans, 60 of whom had PTSD. Resting state fMRI was collected for all participants, parcellated into seven a priori functional networks, and functional connectivity was computed for all within and between network pairs. Plasma assays were performed for a comprehensive panel of 9 neurosteroids.

Exploratory generalized linear models were conducted to predict differences in two networks previously found to be related to PTSD, namely the cortical limbic-frontal parietal control (FPCN) and within-limbic network. Connectivity was predicted, Clinician Administered PTSD Scale (CAPS) severity score, plasma biomarker, and CAPS x Biomarker interaction.

Results: Two biotypes of PTSD affecting limbic-FPCN and within-limbic connectivity were identified. A significant effect was found for limbic-FPCN functional connectivity for the PTSD x norepinephrine (NE) interaction (p = .016). Decomposition of this interaction suggested that individuals with PTSD and high NE had significantly reduced limbic-FPCN connectivity than individuals either without PTSD or with PTSD and low NE. Next, a significant effect was found for within-limbic functional connectivity for a PTSD x cortisol interaction (p = .014). Here, individuals with PTSD and low cortisol had increased within-limbic network connectivity relative to those without PTSD or with PTSD and high cortisol.

Conclusions: These preliminary findings suggest the existence of two neuromolecular biotypes of PTSD that predict dysfunction in neural networks related to maladaptive functional and cognitive outcomes and could inform precision medicine approaches to treatment.

Live Zoom Session – April 21st

research Areas

Authors

Meghan Pierce, Ph.D., Audreyana Rickels, Ph.D., David Rothlein, Ph.D., Anna Stumps, B.A., Regina McGlinchey, Ph.D., Michael Esterman, Ph.D.