Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure

Eur Heart J. 2024 May 21;45(19):1753-1764. doi: 10.1093/eurheartj/ehae149.

Abstract

Background and aims: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis.

Methods: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala).

Results: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score.

Conclusions: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.

Keywords: Atherosclerosis; Cardiovascular disease; Cortico-limbic system; Magnetic resonance imaging; Post-traumatic stress disorder; Stress.

MeSH terms

  • Adult
  • Amygdala / diagnostic imaging
  • Amygdala / physiopathology
  • Carotid Artery Diseases* / diagnostic imaging
  • Carotid Artery Diseases* / physiopathology
  • Case-Control Studies
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Positron-Emission Tomography*
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / physiopathology
  • Radiopharmaceuticals
  • Stress Disorders, Post-Traumatic* / diagnostic imaging
  • Stress Disorders, Post-Traumatic* / physiopathology
  • Stress, Psychological / complications
  • Stress, Psychological / physiopathology