A potential link between inflammation and the structure of specific regions of the brain has been identified by researchers at the University of Birmingham’s Institute for Mental Health and Institute of Cancer and Genomic Sciences, with collaborators from the MRC Biostatistics Unit, University of Manchester and University of Bristol.

The study, published today in JAMA Psychiatry, may be particularly relevant for neurodevelopmental psychiatric disorders including autism spectrum and schizophrenia.

Researchers say the findings could open up a completely new target for the pharmacological treatment of these disorders, which has not significantly changed since the identification of antipsychotic medications in the mid-late 20th century.

The research showed that genes associated with inflammation, particularly interleukin (IL) 6, are linked to a reduction in grey matter volume in certain areas of the brain known to be implicated in neuropsychiatric disorders.

Using records from the UK Biobank, a large-scale biomedical database, the team was able to compare genetic variants which affect levels of IL-6, and other inflammatory genes in more than 20,000 patients with changes in grey matter volume in specific areas of the brain.

They were able to show strong links between IL-6 and brain structure particularly in the temporal and frontal regions. Further analysis using the Allen Human Brain Atlas, showed that genes overexpressed in these areas are associated with conditions such as epilepsy, cognitive disfunction, and schizophrenia.

Stephen Burgess, group leader at the MRC Biostatistics Unit and co-author said:

By demonstrating statistical associations between genetic factors affecting the regulation of inflammatory pathways and grey matter volume in specific brain regions, this investigation provides further clues which link inflammation with mental health. This increases our understanding of the biological processes involved in mental health, and points towards potential therapy targets for treating schizophrenia.”

The work is part of the PIMS (Psychosis Immune Mechanism Stratified Medicine Study) programme, led by the University of Birmingham and University of Bristol, and set up to investigate the links between inflammation and psychosis. In the next phase of the research, the group will carry out experimental studies to knock out IL-6, as well as replicating the Biobank research in more diverse patient cohorts.

Read full paper published in JAMA Psychiatry.

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