The role of tight junction proteins in the pathogenesis of schizophrenia.

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.