Alterations in Peripheral C-Reactive Protein and Inflammatory Cytokine Levels in Patients with Panic Disorder: A Systematic Review and Meta-Analysis

Background: Accumulating evidence has shown the important role of the inflammatory process in the pathophysiology of mental disorders. However, the relative levels of inflammatory markers in patients with panic disorder (PD) have rarely been evaluated. The aim of the present study was to conduct a systematic review to determine the correlation of peripheral C-reactive protein (CRP) and inflammatory cytokine profiles with PD. Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for quantitative research studies published up to July 31, 2021 that measured peripheral levels of CRP and inflammatory cytokines in people with PD compared with controls. Meta-analysis using a random-effects model was performed for the levels of CRP and inflammatory cytokines with data from three or more studies. Results: Fourteen identified studies met the inclusion criteria. In total, 18 cytokines were evaluated. Markers that were reported in more than 3 studies were included in this metaanalysis. The results showed that peripheral levels of CRP, IL-6, IL-2 and TNF-alpha were significantly higher in PD patients than in healthy controls, while there was no significant difference in peripheral levels of IL-1 beta, IL-10 and IFN-gamma between groups. Notably, the relevant studies involving IL-6, IL-1 beta, IL-10 and IFN-gamma in PD patients were highly heterogeneous. Similar to meta-analyses of other inflammatory factors in mental disorders, our meta-analysis also reflected differences in participant medication use, comorbid anxiety or depression, sampling methods and detection methods. Eight inflammatory cytokines were reported in only one study, and their expression levels were higher, lower, or unchanged compared with those in healthy controls. Conclusion: There is preliminary evidence to suggest a significant inflammatory response in PD patients, but the role of inflammatory markers in PD remains unclear. Studying inflammatory markers in PD will help to clarify the etiology and pathophysiological mechanisms of the disorder.