Reininghaus Eva Z, Lackner Nina, Birner Armin, Bengesser Susanne, Fellendorf Frederike T, Platzer Martina, Rieger Alexandra, Queissner Robert, Kainzbauer Nora, Reininghaus Bernd, McIntyre Roger S, Mangge Harald, Zelzer Sieglinde, Fuchs Dietmar, Dejonge Silvia, Müller Norbert
Department of Psychiatry, Medical University of Graz, Graz, Austria.
Department of Psychology, Karl-Franzens University of Graz, Graz, Austria.
Bipolar Disord. 2016 Mar;18(2):155-63. doi: 10.1111/bdi.12380.
Matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) are both involved in the restructuring of connective tissues. Evidence also implicates MMP9 and sICAM in cardiovascular and neoplastic diseases, where blood levels may be a marker of disease severity or prognosis. In individuals with bipolar disorder (BD), higher risk for cardiovascular illness has been extensively reported.
The aim of this investigation was to measure and compare peripheral levels of serum MMP9 and sICAM in adults with euthymic BD and healthy controls (HC). Furthermore, we focussed on correlations with illness severity and metabolic parameters.
MMP9 levels among the BD sample (n = 112) were significantly higher than among the HC (n = 80) (MMP9: F = 9.885, p = 0.002, η(2) = 0.058) after controlling for confounding factors. Patients with BD in a later, progressive stage of disease showed significantly higher MMP9 as well as sICAM-1 levels compared to patients with BD in an earlier stage of disease (MMP9: F = 5.8, p = 0.018, η(2) = 0.054; sICAM-1: F = 5.6, p = 0.020, η(2) = 0.052). Correlation analyses of cognitive measures revealed a negative association between performance on the d2 Test of Attention and MMP9 (r = -0.287, p = 0.018) in the BD sample. Despite the sample being euthymic (i.e., according to conventional criteria) at the time of analysis, we found significant correlations between MMP9 as well as sICAM-1 and subthreshold depressive/hypomanic symptoms.
A collection of disparate findings herein point to a role of MMP9 and cICAM-1 in the patho-progressive process of BD: the increased levels of serum MMP9 and sICAM-1, the correlation between higher levels of these parameters, progressive stage, and cognitive dysfunction in BD, and the positive correlation with subthreshold symptoms. As sICAM-1 and MMP9 are reliable biomarkers of inflammatory and early atherosclerotic disease, these markers may provide indications of the presence of occult cardiovascular disease in this highly at-risk population.
基质金属蛋白酶9（MMP9）和可溶性细胞间黏附分子1（sICAM-1）均参与结缔组织重构。有证据表明，MMP9和sICAM也与心血管疾病和肿瘤性疾病有关，其血液水平可能是疾病严重程度或预后的标志物。在双相情感障碍（BD）患者中，心血管疾病的高风险已被广泛报道。
本研究旨在测量和比较处于心境正常的BD成年患者和健康对照（HC）外周血清MMP9和sICAM水平。此外，我们重点关注了其与疾病严重程度和代谢参数的相关性。
在控制混杂因素后，BD样本（n = 112）中的MMP9水平显著高于HC样本（n = 80）（MMP9：F = 9.885，p = 0.002，η(2) = 0.058）。与疾病早期的BD患者相比，处于疾病晚期进展阶段的BD患者的MMP9以及sICAM-1水平显著更高（MMP9：F = 5.8，p = 0.018，η(2) = 0.054；sICAM-1：F = 5.6，p = 0.020，η(2) = 0.052）。认知测量的相关分析显示，BD样本中注意力的d2测试表现与MMP9之间存在负相关（r = -0.287，p = 0.018）。尽管在分析时样本处于心境正常状态（即根据传统标准），但我们发现MMP9以及sICAM-1与阈下抑郁/轻躁狂症状之间存在显著相关性。
本文一系列不同的研究结果表明MMP9和cICAM-1在BD的病理进展过程中发挥作用：血清MMP9和sICAM-1水平升高，这些参数水平升高、疾病进展阶段与BD认知功能障碍之间的相关性，以及与阈下症状的正相关。由于sICAM-1和MMP9是炎症和早期动脉粥样硬化疾病的可靠生物标志物，这些标志物可能提示这一高危人群中隐匿性心血管疾病的存在。
