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

• Published in: Journal of psychiatric research Vol. 129; pp. 189 - 197
• Main Authors: Edberg, David, Hoppensteadt, Debra, Walborn, Amanda, Fareed, Jawed, Sinacore, James, Halaris, Angelos
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2020
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Bipolar disorder; Bipolar Disorder - drug therapy; CCL2; Celecoxib; Celecoxib - therapeutic use; Chemokine CCL2; Cyclooxygenase 2 Inhibitors - therapeutic use; Double-Blind Method; Humans; Inflammation; MCP-1; Treatment Outcome; Treatment-resistant bipolar depression; Bipolar disorder; CCL2; MCP-1; Inflammation; Treatment-resistant bipolar depression; Celecoxib
• ISSN: 0022-3956; 1879-1379; 1879-1379
• DOI: 10.1016/j.jpsychires.2020.06.010

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). 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). 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. 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.