Department of Psychiatry and Behavioral Neuroscience, Loyola University Stritch School of Medicine, Chicago, IL, USA.
Department of Pathology, Loyola University Stritch School of Medicine, Chicago, IL, USA.
J Psychiatr Res. 2020 Oct;129:189-197. doi: 10.1016/j.jpsychires.2020.06.010. Epub 2020 Jul 30.
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.
神经炎症在双相情感障碍抑郁（BDD）的病理生理学中起作用，并且已经报道了炎症介质水平的改变，例如单核细胞趋化蛋白-1（MCP-1，也称为 CCL2）。本研究专门报告了 MCP-1 水平，作为接受环氧化酶-2 抑制剂塞来昔布（CBX）联合治疗的患者的 BDD 和/或治疗反应的潜在标志物。
在这项随机、10 周、双盲、双臂、安慰剂对照研究中，47 名治疗抵抗性 BDD 患者接受了艾司西酞普兰（ESC）+CBX 或 ESC+安慰剂（PBO）治疗。在 BDD 受试者和健康对照组（HC）中，在 3 个时间点测量了血浆 MCP-1 水平。使用汉密尔顿抑郁量表（HAMD-17）量化抑郁严重程度。
与 PBO 相比，CBX 组在第 4 周（P=0.026）和第 8 周（P=0.002）的 HAMD-17 评分显著降低。BDD 与 HC 受试者在基线时的 MCP-1 水平无显著差异（P=0.588），第 8 周时 CBX 与 PBO 组之间的 MCP-1 水平也无显著差异（P=0.929）。在 CBX 或 PBO 治疗无反应者中，第 8 周的 HAMD-17 评分和 MCP-1 水平呈显著负相关（P=0.050）。无反应者在第 4 周（P=0.049）和第 8 周（P=0.014）时的 MCP-1 水平显著低于有反应者。MCP-1 与 PBO 组中的促炎分析物呈正相关，与 CBX 组中的抗炎分析物呈正相关。
联合治疗降低了治疗抵抗性，并增强了抗抑郁反应。BDD 患者的基线血浆 MCP-1 水平未改变。由于无反应者的 MCP-1 水平较低，因此升高的 MCP-1 可能表明对 CBX+SSRI 治疗的反应更好。
