The Blood-Brain Barrier in Bipolar Disorders: A Systematic Review

Clara Wakonigg Alonso, Frances McElhatton, Brian O’Mahony, Matthew Campbell, Thomas Pollak, Paul Stokes

Research output: Contribution to journalReview articlepeer-review

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Background: 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

Methods: 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.

Results: 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.

Limitations: 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.

Conclusions: 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.
Original languageEnglish
JournalJournal of Affective Disorders
Publication statusAccepted/In press - 14 Jun 2024


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