Institute of Psychiatry & Psychology and Neuroscience, King's College London,United Kingdom.
Institute of Psychiatry & Psychology and Neuroscience, King's College London,United Kingdom.
J Affect Disord. 2024 Sep 15;361:434-444. doi: 10.1016/j.jad.2024.06.032. Epub 2024 Jun 17.
Bipolar disorders (BD) are chronic, debilitating disorders. The blood-brain barrier (BBB) has been increasingly investigated in BD. This systematic review aimed to assess the available evidence on the relationship between BD and markers of BBB dysfunction.
A systematic search in PubMed, Embase, PsycINFO, CINAHL and Web of Science was run where the primary outcomes were BBB markers such as S100B, albumin ratio, matrix metalloproteinase (MMP), cell adhesion molecule (CAM), and tight junction proteins. Techniques included blood, cerebrospinal fluid (CSF), post-mortem, genetic and imaging methods in BD compared to healthy controls.
55 studies were identified, 38 of which found an association between BD and markers of BBB dysfunction. 16/29 studies found increased blood/CSF albumin ratio, S100B, CAMs or MMP levels in BD participants compared to controls. 5/19 post-mortem studies found increased levels of chondroitin sulphate proteoglycans, intercellular CAM, neurexin or claudin-5 mRNA in distinct locations throughout the brain in BD compared to controls. One imaging study identified extensive BBB leakage in 30 % of BD participants, compared to 0 % in controls.
The diversity in methodologies used in the included studies makes direct comparison of results challenging. Furthermore, imaging methods are the gold standard, but only one study used them. Other markers are only indicative of BBB permeability.
This review suggests an association between BD and BBB dysfunction. Further research is needed to provide definite answers considering the existing literature's limitations, and to clarify whether this association provides a pathogenic mechanism, or is an epiphenomenon of BD.
双相情感障碍（BD）是一种慢性、使人虚弱的疾病。血脑屏障（BBB）在 BD 中的研究越来越多。本系统评价旨在评估 BD 与 BBB 功能障碍标志物之间关系的现有证据。
在 PubMed、Embase、PsycINFO、CINAHL 和 Web of Science 中进行了系统搜索，主要结果是 BBB 标志物，如 S100B、白蛋白比率、基质金属蛋白酶（MMP）、细胞黏附分子（CAM）和紧密连接蛋白。技术包括在 BD 患者中与健康对照组相比的血液、脑脊液（CSF）、尸检、遗传和成像方法。
确定了 55 项研究，其中 38 项研究发现 BD 与 BBB 功能障碍标志物之间存在关联。16/29 项研究发现 BD 患者的血液/CSF 白蛋白比率、S100B、CAM 或 MMP 水平高于对照组。5/19 项尸检研究发现 BD 患者大脑不同部位的软骨素硫酸盐蛋白聚糖、细胞间 CAM、神经连接蛋白或紧密连接蛋白 5 的 mRNA 水平升高，而对照组则没有。一项成像研究发现，30%的 BD 患者存在广泛的 BBB 渗漏，而对照组则为 0%。
纳入研究中使用的方法多样性使得结果难以直接比较。此外，成像方法是金标准，但只有一项研究使用了它们。其他标志物仅表明 BBB 通透性。
本综述表明 BD 与 BBB 功能障碍之间存在关联。鉴于现有文献的局限性，需要进一步研究以提供明确的答案，并阐明这种关联是否提供了一种发病机制，或者是否是 BD 的一种伴随现象。
