Plasma MCP-1 levels in bipolar depression during cyclooxygenase-2 inhibitor combination treatment.

Abstract: Background Neuroinflammation plays a role in the pathophysiology of Bipolar Disorder Depression (BDD) and altered levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1, aka CCL2) have been reported. This study reports specifically on MCP-1 levels, as a potential marker of BDD and/or treatment response in patients receiving combination treatment with the cyclooxygenase-2 inhibitor, celecoxib (CBX). Methods In this randomized, 10-week, double-blind, two-arm, placebo-controlled study, 47 patients with treatment resistant BDD received either escitalopram (ESC) + CBX, or ESC + placebo (PBO). Plasma MCP-1 levels were measured at 3 time points in the BDD subjects, and in a healthy control (HC) group. Depression severity was quantified using the Hamilton Depression Scale (HAMD-17). Results The CBX group had significantly lower HAMD-17 scores vs. PBO at week 4 (P=0.026) and week 8 (P=0.002). MCP-1 levels were not significantly different in BDD vs. HC subjects at baseline (P=0.588), nor in CBX vs. PBO groups at week 8 (P=0.929). Week 8 HAMD-17 scores and MCP-1 levels were significantly negatively correlated in treatment non-responders to CBX or PBO (P=0.050). Non-responders had significantly lower MCP-1 levels vs. responders at weeks 4 (P=0.049) and 8 (P=0.014). MCP-1 was positively correlated with pro-inflammatory analytes in the PBO group and with anti-inflammatory analytes in the CBX group. Conclusions Combination treatment reduced treatment resistance and augmented antidepressant response. Baseline plasma MCP-1 levels were not altered in BDD patients. Since non-responders had lower levels of MCP-1, elevated MCP-1 may indicate a better response to CBX + SSRI treatment.