Immune cells associated with schizophrenia

Scientists at Neuroscience Research Australia (NeuRA) have identified immune cells in greater amounts in the brains of some people with schizophrenia — a major breakthrough that has the potential to transform global schizophrenia research and open new avenues for developing targeted immune cell therapies.

No single cause of schizophrenia has ever been identified, and this has prevented the development of a cure. Current treatments for schizophrenia are designed to suppress symptoms rather than target underlying causes of the disorder, and can produce unwanted side effects.

According to NeuRA’s Professor Cynthia Shannon Weickert, most scientists have a long-held belief that immune cells are independent from the brain pathology in psychotic illnesses. “In our study,” she said, “we challenged this assumption that immune cells were independent of the brain in psychiatric illness and made an exciting discovery. We identified immune cells as a new player in the brain pathology of schizophrenia.”

Current schizophrenia research has focused on the status of three brain cells: the neurons; the glial cells, which support the neurons; and the endothelial cells, which coat the blood vessels. Employing new molecular techniques, Prof Shannon Weickert and her team identified the presence of a fourth cell — the macrophage, a type of immune cell in the brain tissue of people with schizophrenia who show high levels of inflammation.

“Immune cells have previously been ignored as they had long been viewed simply as travellers just thought to be passing by, undertaking surveillance work,” said Prof Shannon Weickert. “Red and white blood cells … were not considered to be residents of the brain, nor were they thought of as visitors dropping in to mix with the resident cells. So they have never been a suspect — until now.

“We have observed in people with schizophrenia, the glial cells … become inflamed and produce distress signals which change the status of the endothelial cells. We think this may cause the endothelial cells to extend sticky tentacles, so when the immune cells travel by some are captured. These cells may transmigrate across the blood–brain barrier, entering the brain in greater amounts in some people with schizophrenia compared to people without the disorder.

“To find immune cells along the blood–brain barrier in increased amounts in people with schizophrenia is an exciting discovery. It suggests immune cells themselves may be producing these inflammatory signals in the brains of people living with schizophrenia.”

Published in the journal Molecular Psychiatry, the discovery shows that specific immune cells are in the brains of some people with schizophrenia in close enough proximity to the neurons to do damage. According to Prof Shannon Weickert, “It suggests that the pathology of schizophrenia could be within the immune cells, and these cells could be triggering the symptoms of psychosis.

“These findings suggest we need to look at whole new avenues of therapy to dampen down the immune system in a variety of ways, or to block the entry of the immune cells into the brain.”

Prof Shannon Weickert is now encouraging a cross-collaborative approach between neuroscientists and immunologists globally, to work together to develop treatments targeting this abnormal immune pathology of schizophrenia.

“This has been my life’s goal: to discover the cause of schizophrenia, to support those living with the disease and their families,” she said. “We hope to have the results of our latest clinical trials released later this year, so stay tuned.”

Image caption: NeuRA’s Professor Cynthia Shannon Weickert and Helen Cai.