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Bhatt, Shivani; Hillmer, Ansel T; Girgenti, Matthew J; Rusowicz, Aleksandra; Kapinos, Michael; Nabulsi, Nabeel; Huang, Yiyun; Matuskey, David; Angarita, Gustavo A; Esterlis, Irina; Davis, Margaret T; Southwick, Steven M; Friedman, Matthew J; Duman, Ronald S; Carson, Richard E; Krystal, John H; Pietrzak, Robert H; Cosgrove, Kelly P
Nature communications, 05/2020, Volume: 11, Issue: 1Journal Article
Despite well-known peripheral immune activation in posttraumatic stress disorder (PTSD), there are no studies of brain immunologic regulation in individuals with PTSD. CPBR28 Positron Emission Tomography brain imaging of the 18-kDa translocator protein (TSPO), a microglial biomarker, was conducted in 23 individuals with PTSD and 26 healthy individuals-with or without trauma exposure. Prefrontal-limbic TSPO availability in the PTSD group was negatively associated with PTSD symptom severity and was significantly lower than in controls. Higher C-reactive protein levels were also associated with lower prefrontal-limbic TSPO availability and PTSD severity. An independent postmortem study found no differential gene expression in 22 PTSD vs. 22 controls, but showed lower relative expression of TSPO and microglia-associated genes TNFRSF14 and TSPOAP1 in a female PTSD subgroup. These findings suggest that peripheral immune activation in PTSD is associated with deficient brain microglial activation, challenging prevailing hypotheses positing neuroimmune activation as central to stress-related pathophysiology.
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