Microglia- mediated neuroimmune suppression in PTSD is associated with anhedonia

• 成果类型: Article
• 署名作者: Bonomi, Robin; Hillmer, Ansel T.; Woodcock, Eric; Bhatt, Shivani; Rusowicz, Aleksandra; Angarita, Gustavo A.; Carson, Richard E.; Davis, Margaret T.; Esterlis, Irina; Nabulsi, Nabeel; Huang, Yiyun; Krystal, John H.; Pietrzak, Robert H.; Cosgrove, Kelly P.
• 署名单位: Yale University; Yale University; Yale University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Connecticut Healthcare System
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14643
• DOI: 10.1073/pnas.2406005121
• 发表日期: 2024-08-27
• 关键词: posttraumatic-stress-disorder; translocator protein tspo; c-reactive protein; dimensional structure; viral suppression; in-vivo; brain; activation; neuroinflammation; plasticity

摘要

Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [11C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age- matched controls. The PTSD group exhibited a significantly lower magnitude LPS- induced increase in TSPO availability in an a priori prefrontal- limbic circuit compared to controls. Greater anhedonic symptoms in the PTSD group were associated with a more suppressed neuroimmune response. In addition, while a reduced granulocyte-macrophage colony- stimulating factor response to LPS was observed in the PTSD group, other measured cytokine responses and self- reported sickness symptoms did not differ between groups; these findings highlight group differences in central-peripheral immune system relationships. The results of this study provide evidence of a suppressed microglia- mediated neuroimmune response to a direct immune system insult in individuals with PTSD that is associated with the severity of symptoms. They also provide further support to an emerging literature challenging traditional concepts of microglial and immune function in psychiatric disease. Significance Using advanced neuroimaging techniques, we show that individuals with posttraumatic stress disorder (PTSD) have a suppressed response to a direct immune insult compared to those without PTSD. Imaging a protein in the brain that is present on glial cells before and after lipopolysaccharide administration, we found that the immune system of individuals with PTSD is compromised relative to controls. This finding suggests that treatments to restore the immune response and regulation of related systems should be considered in future clinical trials.