Chemokine alterations in bipolar disorder: A systematic review and meta-analysis

We aimed to perform a systematic review and meta-analysis of studies examining the levels of chemokines in peripheral blood of patients with bipolar disorder (BD) and healthy controls. Meta-analysis was based on random-effects models with Hedges' g as the effect size estimate. We included 13 eligible studies (1221 BD patients and 663 controls). The following chemokines were analysed: interleukin-8 (IL-8), monocyte-chemoattractant protein-1 (MCP-1), eotaxin-1, eotaxin-2 and interferon-γ-induced protein 10 (IP-10). The levels of IL-8 (N = 8, g = 0.26, 95%CI: 0.11-0.41, p < 0.001), MCP-1 (N = 8, g = 0.40, 95%CI: 0.18-0.63), eotaxin-1 (N = 3, g = 0.55, 95%CI: 0.21-0.89, p = 0.001) and IP-10 (N = 4, g = 0.95, 95%CI: 0.67-1.22, p < 0.001) were significantly higher in BD patients as compared with controls. Subgroup analyses revealed that elevated levels of IL-8 (N = 5, g = 0.75, 95%CI: 0.42-1.07, p < 0.001) and MCP-1 (N = 4, g = 0.57, 95%CI: 0.28-0.86, p < 0.001) appeared only in BD patients during their depressive phase. Illness duration was associated with significantly lower levels of IL-8 in meta-regression analysis. In turn, elevated levels of IP-10 were present during euthymia (N = 2, g = 0.76, 95%CI: 0.43-1.10, p < 0.001) but not depression (N = 2, g = 1.81, 95%CI: -0.16 to 3.77, p = 0.072). The analysis of eotaxin-1 levels was mainly based on studies of euthymic BD patients (N = 3). Our results suggest that chemokine alterations in BD might be related to mood state. Elevated levels of IL-8 and MCP-1 might be specific to depression. Available evidence indicates that increased levels of eotaxin-1 and IP-10 appear in euthymia; however, more studies are needed to address these alterations in other mood states.