Circulating hematopoietic progenitor cell number is associated with prefrontal cortical thickness, white matter integrity and PTSD duration in combat-exposed veterans

Background Circulating hematopoietic progenitor cells (PCs; CD34+ and CD34+/KDR+) facilitate neurogenesis and neovascularization, promoting increased cortical thickness and white matter integrity in animal models. However, it unknown whether low PCs are associated with trauma symptoms or neurovascular health among veterans. Objectives Determine whether lower PCs are associated with: (1) posttraumatic stress disorder (PTSD) diagnosis, duration and symptoms, (2) decreased prefrontal cortical (PFC) thickness, and (3) reduced white matter integrity, indexed by white matter hypointensities (WMH), and tracts relevant to fear processing: the Uncinate Fasciculus (UF) and Inferior Fronto-Occipital Fasciculus (IFOF). Methods 100 male and 8 female combat-exposed veterans reported PTSD symptoms (43 PTSD+) and were studied by 3T MRI, acquiring whole brain T1-weighted images and, for a subsample ( n  = 54), diffusion tensor images. PCs were characterized by flow cytometry. Results Higher CD34+/KDR+ counts were related to greater PFC thickness (DM-PFC and DL-PFC), while higher CD34+ counts were related to better IFOF (but not UF) integrity and fewer WMH, controlling for age, gender, smoking, cardiovascular comorbidities and head injury. In PTSD+ subjects, CD34+/KDR+ counts were inversely related to time since the worst trauma, but not PTSD diagnosis or current symptoms. Conclusions PCs are associated with enhanced white matter integrity and PFC thickness, with potential implications for neurovascular plasticity and fear processing. In patients with PTSD, PCs may exhibit accelerated depletion with increasing time post-trauma.