Blood-brain barrier associated tight junction disruption is a hallmark feature of major psychiatric disorders

Major psychiatric disorders affect 25% of the population. While genetic and environmental risk factors have been identified, the underlying pathophysiology of conditions, such as schizophrenia, bipolar disorder and major depression remains largely unknown. Here, we show that endothelial associated t...

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Bibliographic Details
Published inTranslational psychiatry Vol. 10; no. 1; p. 373
Main Authors Greene, Chris, Hanley, Nicole, Campbell, Matthew
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 02.11.2020
Nature Publishing Group
Subjects
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Behavioral Sciences
Biological Psychology
Blood-brain barrier
Blood-Brain Barrier - metabolism
Claudin-5 - metabolism
Female
Humans
Male
Medicine
Medicine & Public Health
Mental disorders
Mental Disorders - metabolism
Neurosciences
Pharmacotherapy
Psychiatry
Schizophrenia
Tight Junctions - metabolism
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Summary:Major psychiatric disorders affect 25% of the population. While genetic and environmental risk factors have been identified, the underlying pathophysiology of conditions, such as schizophrenia, bipolar disorder and major depression remains largely unknown. Here, we show that endothelial associated tight junction components are differentially regulated at the blood-brain barrier (BBB) in distinct neuroanatomic regions of human donor brain tissues. Previous studies have shown associations between BBB disruption and the development of psychiatric behaviours in rodents. Using immunohistochemistry and qRT-PCR, we show that the expression of claudin-5 is reduced in the hippocampus of individuals diagnosed with major depression or schizophrenia. We also show that levels of tight junction mRNA transcripts, including claudin-5, claudin-12 and ZO-1 correlate with disease duration and age of onset of a range of psychiatric disorders. Together, these data show that BBB associated tight junction disruption and dysregulation is a common pathology observed across the major psychiatric disorders. Targeting and regulating tight junction protein integrity at the BBB could, therefore, represent a novel therapeutic strategy for these conditions.
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ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-020-01054-3