Scientists Say ‘Leaky’ Blood-Brain Barrier Could Contribute To Schizophrenia

Enlightened Solutions

When it comes to the central nervous system (CNS), which is comprised of the brain and spinal cord, the blood-barrier shields it from the immune system. In a new study, a research team is hypothesizing that when this barrier is compromised, it ends up causing inflammation in the brain that can cause schizophrenia as a result.

In order to further investigate the possible connection, researchers took cells from both health individuals, as well as from individuals that have a rare genetic disorder that’s known to increase the risk of schizophrenia. What they found was that the cells that came from the group with rare genetic disorder were more ‘leaky,’ and formed molecules that were more inflammatory.

The World Health Organization (WHO) defines schizophrenia as ‘distortions in thinking, perception, emotions, language, sense of self and behavior. Common experiences include hallucinations (hearing voices or seeing things that are not there) and delusions (fixed, false beliefs).’ These symptoms can also be classified as “positive” such as delusions and hallucinations, or “negative” such as apathy and social withdrawal.

For many years, scientists have wondered if there is a link between schizophrenia and the immune system. What they found was that there is evidence that suggests that inflammation that was brought about by a viral infection, possibly before birth or during someone’s childhood, could actually activate schizophrenia in adulthood.

Other studies have also discovered that some people diagnosed with schizophrenia had changes in their blood-brain barriers.

The blood-brain barrier is described as the ‘tightly packed layer of cells that line the blood vessels in the brain and spinal cord.’ It works to stop blood-borne immune cells from entering the central nervous system and causing infections while also making sure the brain gets vital nutrients at the same time. This process is also known as “immune privilege” on the brain to protect it from possible harmful inflammation.

A research group from the School of Veterinary Medicine at the University of Pennsylvania in Philadelphia looked at whether there is a link between people with compromised blood-brain barrier and DiGeorge syndrome or 22qDS, which is a rare genetic disease or a genetic deletion syndrome, and their heightened possibility of having schizophrenia.

Statistics show that individuals that are born with DiGeorge syndrome ‘have a 1 in 4 risk’ of developing schizophrenia when they get older. This study was compared with the normal overall risk of individuals getting schizophrenia, which is around 1 in 100 in the general adult population.

People diagnosed with 22qDS have a small section of DNA missing from the chromosome 22 of their genome.


A Leaky Barrier

In order to check their hypothesis, the research group took cells from those with DiGeorge syndrome and schizophrenia as well as from those with healthy matched controls. Then, they turned the cells ‘into induced pluripotent stem cells,’ which are cells that can turn into any kind of cell in the body.

Then when in the laboratory, the team converted the stem cells into the kinds of cells that line the blood vessels within the brain. It’s these types of cells that are operate as the blood-brain barrier.

The scientists learned that for the cells that were taken from individuals with DiGeorge syndrome and schizophrenia made a ‘less effective, more “leaky” barrier’ than from those that were taken from the healthy control participants.

Additionally, the cells also generated more of particular molecule that encourages inflammation. As a result, more immune cells managed to penetrate the blood-brain barrier.

Meanwhile, the research group also achieved very similar results when they looked into the integrity of the blood-brain barrier of a mouse that had DiGeorge syndrome.

Moreover, they also did the same tests in brain tissue from three people postmortem that had DiGeorge syndrome, as well as another three healthy controls of the same age. What they discovered was that the effectiveness of the blood-brain barrier of the ones they tested had also been compromised.

The research, which was published in the journal Brain, was led by doctoral student Alexis Crockett.


How About Other Brain Disorders?

What the study authors hypothesize is that a jeopardized blood-brain barrier could possibly risk the increase of psychosis and other brain disorders for those with DiGeorge syndrome when there’s interaction with environmental and other risky genetic factors.

Senior study author, Professor Jorge I. Alvarez from the School of Veterinary Medicine says, “[W]e think these findings could also be used to understand how the blood-brain barrier and neurological processes impact not only schizophrenia but mental disorders at large.”

A report from 2019 shared a study about how brain inflammation and cognitive impairment was seen in in aging mice with faulty blood-brain barriers. What Prof. Alvarez shares is that from the continual research into the link between neuropsychiatric disease and inflammation could hopefully lead to new types of therapy for those dealing with such conditions.

Meanwhile, immunotherapy and anti-inflammatory drugs have managed to show some promise as treatment for schizophrenia, side by side with other typically standard treatments.


Schizophrenia is Labeled as Multifactorial

It’s important to note that schizophrenia is described as a “multifactorial” condition, which means that there is no one clear or single cause. Instead, it’s a multitude of different genetic and environmental influences that can enhance or reduce one’s risk of developing it later on.

What Prof. Alvarez said is that those with DiGeorge syndrome “phenotype,” which is explained as ‘characteristics arising from interactions between genetics and environment,’ could possibly have negative reactions to certain environmental difficulties or concerns.

Alvarez shares, “These might include prenatal infection in the mother, or an infection in childhood.”

He adds, “In terms of a ‘second hit, we believe that such environmental challenges will exacerbate the phenotype described under [steady] conditions,” meaning the “second hit” could actually worsen the condition in particular ways.


Study Limitations

Professor Alvarez and his colleagues also shared their study limitations in their paper as well.

One such limitation is that their experiments weren’t able to prove that all individuals with DiGeorge syndrome had compromised blood-brain barriers. This means that there is a chance that these particular changes are only exhibited by those that eventually develop schizophrenia later on.

Prof. Alvarez explains that to test this possibility, he and his team would need to repeat the experiments by ‘using pluripotent stem cells from people who have this particular genetic deletion syndrome but have not developed schizophrenia.’

Alvarez explains, “[W]e are planning to run these experiments using deleted non-schizophrenia [stem cells].”