C‐Reactive Protein: Marker of risk for post‐traumatic stress disorder and its potential for a mechanistic role in trauma response and recovery

• Published in: The European journal of neuroscience Vol. 55; no. 9-10; pp. 2297 - 2310
• Main Authors: Friend, Samantha F., Nachnani, Rahul, Powell, Susan B., Risbrough, Victoria B.
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01-05-2022
• Subjects: Animal models; Arousal; Avoidance behavior; biomarker; Biomarkers - metabolism; C-Reactive Protein - metabolism; Chronic infection; C‐reactive protein; Gene expression; Humans; Inflammation; Inflammation - complications; Inflammation - metabolism; Post traumatic stress disorder; Proteins; Social interactions; Stress Disorders, Post-Traumatic - diagnosis; Stress response; Trauma; post-traumatic stress disorder; C-reactive protein; biomarker; inflammation
• ISSN: 0953-816X; 1460-9568; 1460-9568
• DOI: 10.1111/ejn.15031

Increasing evidence indicates that inflammation plays a role in PTSD and stress disorder pathophysiology. PTSD is consistently associated with higher circulating inflammatory protein levels. Rodent models demonstrate that inflammation promotes enduring avoidance and arousal behaviors after severe stressors (e.g., predator exposure and social defeat), suggesting that inflammation may play a mechanistic role in trauma disorders. C‐reactive protein (CRP) is an innate acute phase reactant produced by the liver after acute infection and chronic disease. A growing number of investigations report associations with PTSD diagnosis and elevated peripheral CRP, CRP gene mutations, and CRP gene expression changes in immune signaling pathways. CRP is reasonably established as a potential marker of PTSD and trauma exposure, but if and how it may play a mechanistic role is unclear. In this review, we discuss the current understanding of immune mechanisms in PTSD with a particular focus on the innate immune signaling factor, CRP. We found that although there is consistent evidence of an association of CRP with PTSD symptoms and risk, there is a paucity of data on how CRP might contribute to CNS inflammation in PTSD, and consequently, PTSD symptoms. We discuss potential mechanisms through which CRP could modulate enduring peripheral and CNS stress responses, along with future areas of investigation probing the role of CRP and other innate immune signaling factors in modulating trauma responses. Overall, we found that CRP likely contributes to central inflammation, but how it does so is an area for further study.
This review describes our current understanding of how C‐reactive protein (CRP), potentially contributes mechanistically to PTSD pathology. We discuss the mechanisms through which CRP could modulate enduring peripheral and CNS stress responses, along with future areas of investigation probing the role of CRP and other immune signaling factors in modulating trauma responses. Overall, the evidence suggests that CRP can contribute to central inflammation, but how it does so is an area for further study.