Researchers from the University of Pennsylvania have found that people with schizophrenia may have a more permeable blood-brain barrier than people without the condition.
A growing body of evidence is pointing towards the possibility of schizophrenia and other neuropsychiatric conditions arising as the result of neuroinflammatory processes. The present study supports this possibility by showing that impaired blood-brain barrier function in patients diagnosed with schizophrenia may impair the immune system, thus leading to inflammation that alters brain function.
For the study, the researchers focused on a rare condition known as 22q11.2 deletion syndrome (22qDS), in which people are born without a small portion of DNA on chromosome 22. Roughly 25% of people with this syndrome develop schizophrenia later on in life. Of particular interest to the researchers in this study was that one of the missing genes common among people with the syndrome is known to affect the blood-brain barrier.
To begin, the researchers extracted stem cells from 22qDS patients diagnosed with schizophrenia and from healthy controls. They then developed the cells into endothelial cells that regulate the blood-brain barrier. In doing so, they found that the cells belonging to 22qDS patients were more impaired compared to healthy controls. The results were replicated with experiments in mice bred to have a version of 22qDS.
Further investigation found that in both human and mouse models of 22qDS, more immune cells and pro-inflammatory molecules were able to cross the blood-brain barrier. Final validation of the findings was conducted by examining post-mortem brain tissue from three 22qDS patients and three controls. From this, the researchers were able to confirm the link between blood-brain barrier leading to immuno-impairment and 22qDS.
“Because 25% of 22q patients develop schizophrenia, it may be possible that these mechanisms taking place in 22q are applicable to idiopathic schizophrenia,” says Jorge Ivan Alvarez, senior author of the study. “And when 22q patients are studied in detail, up to 80% are found to have some form of mental disorder, so these findings may well extend to other disorders as well.”
The researchers now aim to further explore how the blood-brain barrier works to understand the processes behind its increased permeability. In particular, they plan on focusing on the role of astrocytes, immune cells that normally support brain function.