PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies

Author:

Bhatt ShivaniORCID, ,Hillmer Ansel T.,Girgenti Matthew J.ORCID,Rusowicz AleksandraORCID,Kapinos Michael,Nabulsi NabeelORCID,Huang Yiyun,Matuskey DavidORCID,Angarita Gustavo A.,Esterlis Irina,Davis Margaret T.,Southwick Steven M.,Friedman Matthew J.ORCID,Duman Ronald S.ORCID,Carson Richard E.ORCID,Krystal John H.,Pietrzak Robert H.,Cosgrove Kelly P.ORCID

Abstract

AbstractDespite well-known peripheral immune activation in posttraumatic stress disorder (PTSD), there are no studies of brain immunologic regulation in individuals with PTSD. [11C]PBR28 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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of Mental Health

Gustavus and Louise Pfeiffer Research Foundation

VA National Center for PTSD

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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