Meixensberger Sophie, Kuzior Hanna, Fiebich Bernd L, Süß Patrick, Runge Kimon, Berger Benjamin, Nickel Kathrin, Denzel Dominik, Schiele Miriam A, Michel Maike, Maier Simon, Bechter Karl, Domschke Katharina, Tebartz van Elst Ludger, Endres Dominique
Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
Department of Psychiatry and Psychotherapy, Medical Center, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
Diagnostics (Basel). 2021 Jun 22;11(7):1134. doi: 10.3390/diagnostics11071134.
Immunological explanatory approaches are becoming increasingly important in schizophrenia research. In this context, the function of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) plays an essential role. Different adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), are key elements in sustaining the integrity of the BBB and BCSFB. The objectives of this study were to (1) compare the levels of different cell adhesion molecules in the CSF of patients with schizophrenia spectrum disorders to those of patients with unipolar depression and (2) analyze their association with the established markers of the BBB/BCSFB function (CSF total protein and albumin quotient (AQ)). Therefore, a total of 40 patients with schizophrenia spectrum disorder and 39 age- and sex-matched control patients with unipolar depression were analyzed. The levels of soluble ICAM-1 (s-ICAM-1), soluble VCAM-1 (s-VCAM-1), and plasminogen activator inhibitor 1 (PAI-1) in the CSF were measured using a magnetic bead multiplexing immunoassay. The levels of sICAM-1 ( < 0.001), sVCAM-1 ( < 0.001), and PAI-1 ( < 0.001) in the CSF were significantly higher in patients with schizophrenia spectrum disorder than in patients with unipolar depression. In addition, a significant correlation of sVCAM-1 levels with total protein concentrations (r = 0.454, = 0.003) and AQ levels (r = 0.512, = 0.001) in patients with schizophrenia spectrum disorders was observed. The results revealed that sICAM-1 and sVCAM-1 levels in the CSF were higher in patients with schizophrenia spectrum disorder than in those with depression. These circulating signaling molecules may indicate endothelial dysfunction causing impaired BBB/BCSFB function in patients with schizophrenia spectrum disorders. Consistent with this view, a highly significant correlation of sVCAM-1 with CSF protein and AQs was detected. Upregulation of these cell adhesion molecules might be indicative of a proinflammatory immune response underlying the BBB/BCSFB disturbance in a subgroup of patients with schizophrenia spectrum disorders. The significance of the study is limited by its retrospective research design and by the absence of a healthy control group. The assay used was not previously established for the measurement of CSF. Further translational and controlled studies of the role of different cell adhesion molecules in schizophrenia are needed.
免疫解释方法在精神分裂症研究中变得越来越重要。在这种背景下，血脑屏障（BBB）和血脑脊液（CSF）屏障（BCSFB）的功能起着至关重要的作用。不同的黏附分子，如细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1），是维持BBB和BCSFB完整性的关键要素。本研究的目的是：（1）比较精神分裂症谱系障碍患者脑脊液中不同细胞黏附分子的水平与单相抑郁症患者的水平；（2）分析它们与已确立的BBB/BCSFB功能标志物（脑脊液总蛋白和白蛋白商数（AQ））的关联。因此，共分析了40例精神分裂症谱系障碍患者和39例年龄及性别匹配的单相抑郁症对照患者。使用磁珠多重免疫测定法测量脑脊液中可溶性ICAM-1（s-ICAM-1）、可溶性VCAM-1（s-VCAM-1）和纤溶酶原激活物抑制剂1（PAI-1）的水平。精神分裂症谱系障碍患者脑脊液中sICAM-1（<0.001）、sVCAM-1（<0.001）和PAI-1（<0.001）的水平显著高于单相抑郁症患者。此外，在精神分裂症谱系障碍患者中观察到sVCAM-1水平与总蛋白浓度（r = 0.454，P = 0.003）和AQ水平（r = 0.512，P = 0.001）之间存在显著相关性。结果显示，精神分裂症谱系障碍患者脑脊液中的sICAM-1和sVCAM-1水平高于抑郁症患者。这些循环信号分子可能表明内皮功能障碍导致精神分裂症谱系障碍患者的BBB/BCSFB功能受损。与此观点一致，检测到sVCAM-1与脑脊液蛋白和AQs之间存在高度显著的相关性。这些细胞黏附分子的上调可能表明在一部分精神分裂症谱系障碍患者中，BBB/BCSFB紊乱存在促炎免疫反应。本研究的意义受到其回顾性研究设计以及缺乏健康对照组两方面的限制。所使用的检测方法之前未被确立用于测量脑脊液。需要对不同细胞黏附分子在精神分裂症中的作用进行进一步的转化研究和对照研究。
