Abstract 14065: Functional and Structural Alterations in Stress-Related Neural Networks Implicated in Atherosclerosis

Introduction: While a link between chronic stress and cardiovascular disease (CVD) is well established, the neurocircuit alterations underlying this association remain unclear. We leveraged advanced multimodal imaging to gain insights into neurocircuit alterations that associate with atherosclerosis. Methods: Individuals with posttraumatic stress disorder (PTSD), trauma-exposed controls without PTSD (TC), and healthy controls (HC) were prospectively enrolled. Participants underwent whole-body 18 F-fluorodeoxyglucose positron emission tomography/magnetic resonance (FDG-PET/MR) imaging. Stress-related neural network activity (SNNA) was assessed on PET as amygdala metabolic activity relative to regulatory (ventromedial prefrontal cortex [vmPFC]) activity. The structural integrity of the uncinate fasciculus, the major white matter tract connecting the amygdala to vmPFC, was assessed using diffusion tensor imaging (DTI). Atherosclerotic burden was assessed on MR as vessel normalized wall index and standard deviation (SD) of vessel wall thickness. Results: Of 91 participants (24 PTSD, 42 TC, 24 HC), 57% were female, and the median age was 37 years. Compared to controls, individuals with PTSD had higher SNNA (Fig 1A) and lower uncinate fasciculus integrity (Fig 1B). SNNA and uncinate fasciculus integrity were negatively correlated (r = - 0.30, p=0.008). Those with PTSD had higher ascending aorta normalized wall indices (p=0.018, adjusted for Framingham risk score). Notably, the SD of carotid wall thickness correlated positively with SNNA and negatively with uncinate fasciculus integrity (Fig 1C & D). Conclusion: These findings suggest that increases in the amygdala relative to vmPFC metabolic activity or disruptions of their structural interconnections may potentiate atherosclerosis. Interventions targeting this stress-related neural network may reduce adverse brain-heart interactions and related cardiovascular disease burden.