Peripheral protein inflammatory biomarkers in bipolar disorder and major depressive disorder: A systematic review and meta-analysis

Objectives: Bipolar disorder (BD) and major depressive disorder (MDD) are mood disorders. The most frequent clinical presentation of BD and MDD is depression, which contributes to high rates of misdiagnosis between disorders. To support diagnostic discrimination and therapeutic stratification, we aim to perform a systematic review and meta-analysis evaluating peripheral protein inflammatory biomarkers between BD and MDD, with a focus on the depressive state. Methods: We conducted a literature search on PubMed, PsycInfo and Embase with no year/language restrictions. Original studies including human participants with a BD or MDD diagnosis which directly compared levels of peripheral protein inflammatory biomarkers between groups were included. A random effects meta-analysis was performed. Results: 35 studies were included in the systematic review. 9 studies were included in the meta-analysis. The meta-analysis showed IL-7 (p < 0.01) levels were significantly decreased in BD, and IL-9 (p < 0.01), CCL3 (p = 0.03), CCL4 (p = 0.01), CCL5 (p = 0.02) and CCL11 (p = 0.04) levels were significantly increased in BD. Limitations: High heterogeneity and limited dataset size restricted our meta-analysis to a small subset of biomarkers and limited our exploration of the effects of moderator variables. Conclusion: This study found differences in IL-7, IL-9, CCL3, CCL4, CCL5 and CCL11 between BD and MDD in a depressive state. These findings support the notion that inflammation is associated with mood disorder pathophysiology, particularly with respect to T-cell network dysregulation. Further studies can assist in better understanding differences between disorders and work towards clinical applications.