Research led by scientists at the University of Birmingham in the U.K. shows that higher expression of the inflammatory biomarker interleukin (IL)-6 can influence brain structure in regions of the brain linked to conditions such as autism spectrum disorder and schizophrenia.
The results support earlier findings showing high levels of IL-6 and related inflammatory proteins in samples taken from patients before the onset of psychosis. Inflammation has also been observed in Alzheimer’s disease patients. The team believes this finding shows some of these conditions may be triggered by inflammation, which, if confirmed, could help experts develop new therapeutic strategies for these conditions.
The study, published in JAMA Psychiatry, included 20,688 participants in the UK Biobank with clinical, genomic and neuroimaging data available and also RNA microarray and other data from six postmortem brains from neurotypical individuals included in the Allen Human Brain Atlas.
The researchers assessed whether levels of five biomarkers –IL-6, IL-1, IL-2, C-reactive protein (CRP), or brain-derived neurotrophic factor (BDNF) linked with inflammation were associated with gray matter in different parts of the brain
The results showed that levels of IL-6, but not the other biomarkers, appear to influence gray matter volume and cortical thickness. This was particularly noticeable in the middle temporal gyrus and superior frontal regions of the brain, areas linked to a number of different neuropsychiatric conditions including epilepsy, cognitive disfunction, and schizophrenia.
“Brain-wide coexpression analysis showed a highly interconnected network of genes preferentially expressed in the middle temporal gyrus, which further formed a highly connected protein-protein interaction network with IL-6,” explain the authors.
Commenting on the work in a press statement, Rachel Upthegrove, a professor in the University’s Institute for Mental Health and lead author on the paper, 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.”
While there are treatments available for conditions such as schizophrenia, they can have unpleasant side effects and don’t work for everyone meaning there is an ongoing unmet need. “This could be the first new target for severe mental illnesses including schizophrenia identified in more than 60 years,” said Upthegrove.
There have already been attempts to treat people with neuropsychiatric illnesses with anti-inflammatory drugs in various trials. These initial studies had mixed results, but the authors believe this may be because inflammation was not present in all the patients tested.
This study was carried out as part of an ongoing project called PIMS (Psychosis Immune Mechanism Stratified Medicine Study), which was started in 2019. Led by the University of Birmingham, the project aims to thoroughly investigate links between inflammation and psychosis. In addition to the current research, the scientists plan to carry out experimental studies investigating the impact of IL-6 in animal models, as well as replicating the current study in a more ethnically diverse patient cohort.
