Study suggests the immune system triggers the effects of psychosis


Novel research has indicated a correlation between genetic changes that influence the brain’s immune system and psychosis, potentially advancing treatments.

The study, conducted by researchers from the Karolinska Institutet at the University of California, discovered that psychosis might be impacted by genetic changes within the brain’s immune system, with the researchers being optimistic that their findings can help to advance medications for schizophrenia and bipolar disorder.

Their study is published in Molecular Psychiatry.

Insufficient care for psychosis

The symptoms of psychosis are vast; hallucinations, paranoid reactions, and changes in the perception of reality are customary, with around 3% of the population suffering from the illness, of which the majority affected have schizophrenia and bipolar disorder.

The problem with the commonly used antipsychotic medication is that it achieves low efficacy, which has incredibly severe patient outcomes; an example of this was highlighted by Sweden’s Board of Health and Welfare, who estimated that patients with schizophrenia have a life expectancy of 15 years less than average.

Göran Engberg, Professor at the Department of Physiology and Pharmacology at the Karolinska Institutet, said: “It is not entirely known what biological mechanisms cause psychosis, but recent research suggests that immune activation in the brain’s glial cells may be the cause. People with psychosis have elevated levels of kynurenic acid in the brain, a messenger that transmits information from the brain’s immune system to the neurons.”

Analysis of GRK3 protein

Prior genome-wide association studies (GWAS) have signified that the GRK3 protein is expressed in all psychosis patients, achieving this through making genetic changes in the immune system, leading the researchers to analyse which specific parts of the immune system affect the disorder.

The team compiled comprehensive data from mouse samples that were insufficient in the GRK3 protein and examinations of genomes of 70 patients with bipolar disorder and 48 healthy control subjects. They determined that GRK3 spikes the sensitivity of the immune system, which subsequently triggers psychotic effects on the brain, increasing the release of the cytokine IL-1beta and kynurenic acid.

Carl Sellgren, the first author of the study from the Karolinska Institutet, said: “Our experimental data are confirmed through genetic studies where we see a link between psychosis in patients with bipolar disorder and decreased expression of GRK3, which leads to an increased amount of kynurenic acid in the brain.”

The research provides the groundwork for the next generation of psychosis medicine, potentially replacing the currently used methods that have been in operation for over 60 years.

Sophie Erhardt, professor at the Karolinska Institutet and the study’s last author, said: “To develop effective, modern drugs, more knowledge is needed about the mechanisms in the brain that can trigger psychosis.”


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