Futtrup Jesper, Margolinsky Rebecca, Benros Michael Eriksen, Moos Torben, Routhe Lisa Juul, Rungby Jørgen, Krogh Jesper
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Mental Health Centre Copenhagen, University Hospital of Copenhagen, Copenhagen, Denmark.
Brain Behav Immun Health. 2020 Jun 30;6:100102. doi: 10.1016/j.bbih.2020.100102. eCollection 2020 Jul.
Blood-brain barrier (BBB) pathology may be associated with mental disorders. The aim of this systematic review and meta-analysis is to identify, evaluate and summarize available evidence on whether potential biomarkers of BBB pathology are altered in patients with schizophrenia spectrum disorders, major depression and bipolar disorder compared to healthy controls.
The primary outcome is blood S100B, while secondary outcomes include biomarkers in blood and/or cerebrospinal fluid, i.e. albumin ratio, fibrinogen, immunoglobulin G, glial fibrillary acidic protein, amyloid beta (Aβ), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases, endothelial glycocalyx constituents, and cell adhesion molecules (CAMs). A systematic search in PubMed, Embase and PsycINFO resulted in 131 eligible studies, of which 93 were included in the meta-analysis. Meta- and subgroup analyses were undertaken using random-effects modelling. The protocol was a priori registered on PROSPERO (CRD42020152721).
S100B was increased in schizophrenia spectrum disorders (24 studies; 1107 patients; standardized mean difference (SMD) = 0.82; 95% confidence interval (CI) = 0.51 to 1.13; I = 90%), major depression (13 studies; 584 patients; SMD = 0.57; 95% CI = 0.31 to 0.83; I = 73%) and bipolar disorder (4 studies; 142 patients; SMD = 0.55; 95% CI = 0.16 to 0.94; I = 48%). Similarly, numerous secondary outcomes, including albumin ratio, fibrinogen, Aβ, MMPs and CAMs, were altered. Results of the included studies varied considerably, and important confounders were often not accounted for.
The findings implicate occurrence of BBB pathology in patients with schizophrenia spectrum disorders, major depression and bipolar disorder compared to healthy controls. However, definite conclusions cannot be drawn, mainly because the investigated biomarkers are indirect measures of BBB pathology.
血脑屏障（BBB）病理可能与精神障碍有关。本系统评价和荟萃分析的目的是识别、评估和总结关于精神分裂症谱系障碍、重度抑郁症和双相情感障碍患者与健康对照相比血脑屏障病理潜在生物标志物是否改变的现有证据。
主要结局指标是血液中的S100B，次要结局指标包括血液和/或脑脊液中的生物标志物，即白蛋白比率、纤维蛋白原、免疫球蛋白G、胶质纤维酸性蛋白、淀粉样β蛋白（Aβ）、基质金属蛋白酶（MMPs）、金属蛋白酶组织抑制剂、内皮糖萼成分和细胞黏附分子（CAMs）。在PubMed、Embase和PsycINFO数据库进行系统检索，共得到131项符合条件的研究，其中93项纳入荟萃分析。采用随机效应模型进行荟萃分析和亚组分析。该方案已在PROSPERO（CRD42020152721）上预先注册。
精神分裂症谱系障碍患者（24项研究；1107例患者；标准化均数差（SMD）=0.82；95%置信区间（CI）=0.51至1.13；I=90%）、重度抑郁症患者（13项研究；584例患者；SMD=0.57；95%CI=0.31至0.83；I=73%）和双相情感障碍患者（4项研究；142例患者；SMD=0.55；95%CI=0.16至0.94；I=48%）的S100B均升高。同样，包括白蛋白比率、纤维蛋白原、Aβ、MMPs和CAMs在内的许多次要结局指标也发生了改变。纳入研究的结果差异很大，且重要的混杂因素往往未得到考虑。
研究结果表明，与健康对照相比，精神分裂症谱系障碍、重度抑郁症和双相情感障碍患者存在血脑屏障病理改变。然而，由于所研究的生物标志物是血脑屏障病理的间接测量指标，因此无法得出明确结论。
