Peripheral blood levels of C-reactive protein in posttraumatic stress disorder: a systematic review and meta-analysis

Posttraumatic stress disorder (PTSD) was reported to be associated with inflammation. C-reactive protein (CRP) is an important biomarker of systemic inflammation. A series of studies have reported the change of peripheral blood CRP in PTSD. However, the results were controversial. Our aim was to evaluate whether abnormal peripheral blood CRP levels was associated with PTSD using a systematic review and meta-analysis method.

Five databases (PubMed, Embase, Web of Science, Cochrane library and PsycINFO) were searched for available articles published up to 2 May, 2026. Hedges' g with its corresponding 95% confidence interval (CI) was selected to assess the group difference in CRP concentrations, a random effects model or fixed effects model were selected according to the results of heterogeneity test.

A total of 32 studies (39 reports) with 2667 PTSD patients and 8166 controls were included in our analysis. Significantly elevated peripheral blood CRP levels were found in PTSD participants compared with controls (Hedges' g = 0.188, 95% CI 0.080 to 0.296, p = 0.001). Subgroup analysis showed a significant elevation in serum (Hedges' g = 0.208, 95% CI 0.049 to 0.368, p = 0.01) and the female groups (Hedges' g = 0.446, 95% CI 0.043 to 0.849, p = 0.03), but not in plasma (Hedges' g = 0.140, 95% CI -0.051 to 0.331, p = 0.151) and the male groups (Hedges' g = 0.143, 95% CI -0.008 to 0.294, p = 0.063), suggesting that the type of biological sample and gender may influence the observed association. Other subgroup analyses (e.g., control type, PTSD type, detection method and traumatic type) generally showed consistent results. The significance of the association between peripheral blood CRP concentration and PTSD remained unchanged after excluding studies outside the Galbraith plot. Baujat plot identified three studies contribute most to the heterogeneity. Removing any single study verified by sensitivity analysis did not reverse the association. Meta-regression analysis revealed that the association was moderated by mean body mass index (BMI). No obvious publication bias was found in the meta-analysis.

This meta-analysis provides evidence for elevation of peripheral blood CRP in PTSD. However, due to the lack of data on time since trauma in the included studies, the current findings cannot differentiate whether the elevated CRP is an acute phase response to the traumatic event itself or the inflammatory state of chronic PTSD. More well-designed longitudinal studies are required to demonstrate this conclusion in the future.