Yulia Sukhorukova, Yana Zorkina, Alisa Andryushchenko, Georgy Kostyuk
Mental-health Clinic No. 1 named after N.A. Alexeev of Moscow Healthcare Department, Zagorodnoe Highway 2, Moscow, 115191, Russia.
Lomonosov Moscow State University, Moscow, Russia.
Eur Arch Psychiatry Clin Neurosci. 2025 Sep 27. doi: 10.1007/s00406-025-02060-6.
The blood-brain barrier (BBB) integrity is important for central nervous system homeostasis, and dysfunction of its components may contribute to the pathogenesis of various neuropsychiatric disorders, including schizophrenia. An additional factor supporting this hypothesis is the association of schizophrenia with DiGeorge syndrome, in which a deletion of a part of one copy of chromosome 22 (22q11DS) leads to haplonephrenia in the Claudin-5 gene (a tight junction protein that forms the BBB). Individuals with 22q11DS have a 25-fold greater risk of schizophrenia than the population average. The aim of our review was to establish the role of tight junction proteins in the pathogenesis of schizophrenia. For this purpose, a systematic literature search was performed. The first part describes genetic polymorphisms of tight junction proteins and studies of patients with DiGeorge syndrome. The second and third parts of the review focus on the expression of tight junction proteins in postmortem samples and serum. The fourth part of the review describes in vitro studies. The fifth part includes animal studies. Mice models with incomplete absence of the Claudin-5 gene have shown specific behavioral and memory impairments. The final part describes the effects of antipsychotics on tight junction proteins and BBB function. The discussed studies support the role of tight junction proteins in the pathogenesis of schizophrenia and the increased permeability of the BBB. However, the number of studies on this topic is extremely small. This review shows the prospects of studying tight junction proteins in psychiatric diseases.
血脑屏障（BBB）的完整性对于中枢神经系统的稳态至关重要，其组成部分的功能障碍可能导致包括精神分裂症在内的各种神经精神疾病的发病机制。支持这一假说的另一个因素是精神分裂症与DiGeorge综合征的关联，其中22号染色体（22q11DS）的一个拷贝的一部分缺失会导致Claudin-5基因（一种形成血脑屏障的紧密连接蛋白）单倍体缺乏。患有22q11DS的个体患精神分裂症的风险比人群平均水平高25倍。我们综述的目的是确定紧密连接蛋白在精神分裂症发病机制中的作用。为此，进行了系统的文献检索。第一部分描述了紧密连接蛋白的基因多态性以及对DiGeorge综合征患者的研究。综述的第二和第三部分重点关注死后样本和血清中紧密连接蛋白的表达。综述的第四部分描述了体外研究。第五部分包括动物研究。Claudin-5基因不完全缺失的小鼠模型已显示出特定的行为和记忆障碍。最后一部分描述了抗精神病药物对紧密连接蛋白和血脑屏障功能的影响。所讨论的研究支持紧密连接蛋白在精神分裂症发病机制中的作用以及血脑屏障通透性增加。然而，关于这个主题的研究数量极少。这篇综述展示了研究紧密连接蛋白在精神疾病中的前景。
