Nikhil Prasad Fact checked by:Thailand Medical News Team Sep 21, 2026 33 minutes ago
The blood-brain barrier may play a far more active role in major psychiatric disorders than previously recognized, with evidence linking barrier dysfunction to major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia.
A new comparative review examined clinical, molecular, neuroimaging, postmortem, and preclinical evidence published mainly between 2000 and 2026. The researchers included 261 publications, 80% of which were published from 2020 onward.
Evidence suggests blood-brain barrier dysfunction may be an important shared biological feature of depression, bipolar
disorder, and schizophrenia.
A Protective Barrier Under Pressure
The blood-brain barrier (BBB) normally tightly controls what can move from circulating blood into brain tissue. Its endothelial cells are supported by tight-junction proteins, astrocytes, pericytes, and other components of the neurovascular unit. When this system weakens, inflammatory molecules, immune cells, and potentially harmful substances may gain greater access to the brain.
In this
Thailand Medical News report, the review highlights inflammation, oxidative stress, mitochondrial dysfunction, metabolic abnormalities, and disrupted stress-hormone signaling as interconnected processes capable of damaging the BBB.
Different Disorders Show Distinct Warning Signs
In MDD, human imaging studies have identified increased BBB permeability in the prefrontal cortex and hippocampus.
Postmortem findings also show reduced claudin-5 and occludin, proteins that help seal the barrier. Animal experiments strengthen the biological link: reducing claudin-5 allowed peripheral interleukin-6 to enter brain tissue and promoted depression-like behavior after stress.
For bipolar disorder, elevated cerebrospinal fluid-to-serum albumin ratios have been associated with illness duration and manic episodes. Imaging evidence additionally links greater BBB leakage with insulin resistance and more severe illness, suggesting an important metabolic-vascular connection.
Schizophrenia studies have found increased BBB permeability in some patients, including thalamic leakage associated with symptom severity.
Reduced claudin-5, diminished pericyte coverage, inflammatory signaling, and altered vascular regulation may further weaken the barrier.
What the Evidence Means
The researchers caution that BBB abnormalities differ by disorder, brain region, and patient subgroup, and no BBB-directed therapy has yet been tested in a controlled clinical trial. The findings nevertheless suggest that the barrier could eventually provide biomarkers and therapeutic targets connecting systemic inflammation and metabolism with brain dysfunction.
Research institutions: Ben-Gurion University of the Negev, Israel, including its Faculty of Health Sciences, Psychiatry Research Unit, School for Community Health Professions, and School of Brain Sciences and Cognition.
The study findings were published in the peer reviewed journal: Pharma
ceuticals.
https://www.mdpi.com/1424-8247/19/9/1483
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