- Researchers investigated how immune cell function may affect the development of schizophrenia.
- They reported that immune factors in people with schizophrenia affect the growth of blood vessels in the brain.
- Further studies are needed to see whether this mechanism is involved in the development of schizophrenia.
Schizophrenia is a chronic mental disorder. Its symptoms can include disorganized speech, delusions and hallucinations.
About 24 million people have schizophrenia worldwide, less than 1% of the adult population.
What causes the condition remains unknown. Researchers suspect that a combination of genetic, physical, psychological, and environmental factors may play a role.
A growing amount of evidence suggests that schizophrenia may arise from an immune response in the brain.
Understanding more about how immune cells work in the brain in people with schizophrenia could lead to the development of treatments for the condition.
Recently, researchers investigated the role of astrocytes in the development of schizophrenia.
Astrocytes are glial cells – a type of cell that support neurons – that are found in the nervous system. They play a major role in immunity by secreting immune proteins known as cytokines. They also modulate the formation of new blood vessels in the brain – known as vascularization- at the blood-brain barrier.
“We know that glial cells are very important for antioxidant and inflammatory responses in the central nervous system,” Dr. Andrew Farah, a psychiatrist at Novant Health in North Carolina, told Medical News Today.
“Schizophrenia and untreated psychosis involve an inflammatory response, so the theory has long held that perhaps these brains are less well equipped to deal with inflammation,” he added.
In a new study published in the journal Molecular Psychiatry, researchers found that astrocytes may increase inflammation and affect how blood vessels grow in the brain.
Dr. Michael McGrath, a psychiatrist and medical director of the Ohana Addiction Treatment Center in Hawaii who was not involved in the study, told Medical News Today:
“This study adds to the growing research indicating that inflammation is involved in schizophrenia,” he said. “The process of inflammation is very complex and this study adds to the details that may lead to specific targeted anti-inflammatory treatments for biological psychiatric conditions such as schizophrenia.”
How the schizophrenia study was conducted
For the study, the researchers extracted skin samples from three people with schizophrenia and four people without the condition.
They then reprogrammed the cells to become induced pluripotent stem cells (iPSCs) and used them to produce neurons and astrocytes.
Next, the researchers analyzed the proteins in each sample. They found that samples from those with schizophrenia contained higher levels of proinflammatory cytokines.
They also contained different levels of other proteins that indicated less vascularization.
After this, the researchers placed the astrocytes into the vascular region of fertilized chicken eggs to observe how they affect blood vessel formation.
They found that astrocytes from people with schizophrenia produced less vascularization. The same astrocytes also secreted more of a pro-inflammatory cytokine known as interleukin-8 (IL-8).
“Astrocytes are known to regulate the immune response in the central nervous system, so it’s possible that they promote more immature or less efficient vascularization,” Pablo Trindade, Ph.D., an adjunct professor at the Federal University of Rio de Janeiro in Brazil and a study author, said in a press release.
“Our patient-derived astrocytes secreted more interleukin-8 (IL-8) than the controls. IL-8 is proinflammatory and suspected to be the main agent of the vascular dysfunction associated with schizophrenia,” he added.
The study authors noted that their findings demonstrate that astrocytes from those with schizophrenia may alter the thickness of blood vessels in the brain, reducing the passage of metabolites that reach the brain.
They added that astrocytes in people with schizophrenia might alter vascularization in fetal neurodevelopment, leading to early brain circuit malformation and potentially schizophrenia later in life.
“First symptoms of schizophrenia most often occur in young adulthood, but this study implies that some of this neuronal dysfunction may be present as early as fetal development,” Dr. Setphanie Hartselle, a clinical associate professor of psychiatry at Brown University in Rhode Island who was not involved in the study, told Medical News Today.
“This is yet another study indicating that inflammation likely plays an enormous role in brain health and more research in this area may provide ways that medications targeting inflammation may eventually help prevent or treat psychiatric disease,” she noted.
Limitations of the research
Dr. David Merrill, an adult and geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center in California, told Medical News Today:
“This study was conducted in cells derived from just three patients with schizophrenia. It remains to be seen if the findings will hold in a larger sampling of patients or if the findings might differ depending on the particular case,” he said.
Medical News Today spoke with Dr, Omotola K. Ajibade, a psychiatry resident at Ocean University Medical Center in New Jersey who was not involved in the study, about its limitations.
“The authors rightly point out this study is hamstrung by its small sample size,” he said. “While the results may not be generalizable to broader populations of those suffering with schizophrenia, they do pose a lot of interesting avenues for future research.”
“Additionally, many of the experiments were run in cultured media, which is a good approximation for certain cellular environments, but it can’t always replicate the complexity seen in whole organisms,” he noted.
Raphael Wald, Psy.D., a neuropsychologist at Marcus Neuroscience Institute, part of Baptist Health South Florida, who not involved in the study, also told MNT:
“This study focuses on abnormalities at the cellular level. It does not necessarily point us to a direct cause of specific behavioral abnormalities that are expressed in daily life though it certainly suggests a relationship.”
MNT also spoke with Emily Treichler, Ph.D., LCP, a licensed clinical psychologist who also was not involved in the study. She noted that while the study helps understand one component of schizophrenia, many other factors play a role too.
“Once we zoom back out we can see that yes, inflammation is important, and so are genetics, the gut microbiome, perinatal development, early life experiences, and so much more,” she said. “It’s a complex picture, and it’s likely to look different depending on the person. There isn’t necessarily anything to do at this point in terms of treatment, but folks who have questions about inflammation can talk to their doctors, for example about anti-inflammatory diets.”
When asked what these findings may mean for treating schizophrenia, John Cottone, Ph.D., a psychologist in New York who was not involved in the study, told MNT:
“If the findings do legitimately identify faulty astrocytes and immature blood vessels as mediators, leading to the pathology of schizophrenia, this opens a broad new area for early detection of the disease and new treatment approaches, perhaps using stem cell treatments, among others.”
“To this point, the causal factors leading to schizophrenia – on both a genetic and neurological level – have focused on broader, nonspecific factors, but these findings identify more specific problems in neurodevelopment, which can yield more specific treatments and preventative measures,” he concluded.
Source: Read Full Article