Researchers at the University of Birmingham have discovered a possible relationship between inflammation and the anatomy of specific brain regions.
The findings, which were published in JAMA Psychiatry today (30 March 2022), could be particularly useful for neurodevelopmental psychiatric illnesses like autism spectrum disorder and schizophrenia.
The discoveries, according to the researchers, could open up an entirely new target for pharmacological therapy of these diseases, which hasn’t changed much since the discovery of antipsychotic drugs in the mid-late twentieth century.
A team from the University’s Institute for Mental Health and Institute of Cancer and Genomic Sciences conducted the study, which included researchers from the Universities of Cambridge, Manchester, and Bristol.
It was shown that genes connected to inflammation, specifically interleukin (IL) 6, are linked to a decrease in grey matter volume in parts of the brain linked to neuropsychiatric diseases.
The team was able to correlate genetic variations that impact levels of IL-6 and other inflammatory genes in more than 20,000 patients with changes in grey matter volume in specific parts of the brain using records from the UK Biobank, a large-scale scientific database.
This study shows that the IL-6 gene, which we know to be linked to systemic inflammation, also affects brain structure in areas associated with these neuropsychiatric disorders. Understanding these links offers an exciting opportunity to explore new treatments which target IL-6. This could be the first new target for severe mental illnesses including schizophrenia identified in more than 60 years.
Professor Rachel Upthegrove
They were able to demonstrate robust connections between IL-6 and brain anatomy, especially in the temporal and frontal areas.
Using the Allen Human Brain Atlas, researchers discovered that genes over-expressed in these locations are linked to epilepsy, cognitive dysfunction, and schizophrenia.
The paper’s principal author is Professor Rachel Upthegrove of the University’s Institute for Mental Health. She said:
“This study shows that the IL-6 gene, which we know to be linked to systemic inflammation, also affects brain structure in areas associated with these neuropsychiatric disorders. Understanding these links offers an exciting opportunity to explore new treatments which target IL-6. This could be the first new target for severe mental illnesses including schizophrenia identified in more than 60 years.”
Dr. John Williams, of the Institute for Cancer and Genomic Sciences at the University, a first author on the paper, said: “Current treatments for these illnesses act on dopamine, a chemical messenger in the brain associated with mood and attention. These drugs can have side effects, however, and they are not effective in all patients.”
“There are drugs already on the market which target inflammation as well as the opportunity to screen potential new compounds. Finding a new avenue for exploring the links between inflammation, brain structure, and neuropsychiatric disorders is really exciting.”
The research is part of the PIMS (Psychosis Immune Mechanism Stratified Medicine Study) initiative, which was established by the University of Birmingham to look into the relationships between inflammation and psychosis. T
he group will conduct experimental tests to knock out IL-6 in the next phase of the study, as well as replicate the Biobank findings in other varied patient populations.
