Recent research has revealed differences in the brain and peripheral immune responses of individuals with posttraumatic stress disorder (PTSD).
A new study published August 22 in Proceedings of the National Academy of Science and led by researchers at Yale School of Medicine and the Veterans Affairs National Center for PTSD utilized positron emission tomography (PET) imaging with [11C]PBR28, a radiotracer to measure 18-kDa translocator protein (TSPO) to better understand microglia, the resident immune cells in the brain of individuals with PTSD.
In conjunction with peripheral immune responses, PET imaging was done before and after administration of lipopolysaccharide (LPS), a potent immune activator, in individuals both with and without PTSD.
The study included 15 individuals with PTSD and 15 demographically matched controls. It found that individuals with PTSD exhibited a significantly lower magnitude of LPS-induced increase in TSPO, within prefrontal-limbic brain regions as compared to controls. This circuit plays a critical role in emotional regulation and stress responses.
“We found that individuals with PTSD showed a reduced immune activation response in the brain, particularly in areas linked to emotional processing,” said Robin Bonomi, MD, PhD, lead author of the study and adjunct assistant professor of psychiatry. “This suggests that individuals with PTSD have a diminished central immune response to a biological stressor”.
The study also revealed that greater severity of anhedonic symptoms—difficulty experiencing pleasure—was associated with a blunted LPS response among individuals with PTSD. Additionally, greater LPS-induced changes in C-reactive protein, a marker of systemic inflammation, were linked to a more suppressed TSPO response. Consistent with a blunted neuroimmune response to LPS, individuals with PTSD also exhibited a blunted granulocyte-macrophage colony-stimulating factor cytokine response relative to controls.
“These findings suggest that both central and peripheral immune stress responses are suppressed in individuals with PTSD,” said Kelly Cosgrove, PhD, senior author of the study and professor of psychiatry, neuroscience, and radiology & biomedical imaging at Yale. “This highlights the importance of examining the role of the immune system in the pathophysiology of PTSD, and whether interventions targeting the immune system might offer new avenues for the treatment of this disorder.”
Other Yale-affiliated authors of the study included Ansel Hillmer, Shivani Bhatt, Aleksandra Rusowicz, Gustavo Angarita, Richard Carson, Margaret Davis, Irina Esterlis, Nabeel Nabulsi, Yiyun Huang, John Krystal, and Robert Pietrzak.