New Evidence Connects Psychosis to the Immune System of the Brain

New Evidence Connects Psychosis to the Immune System of the Brain

According to Oxford University researchers, some patients sectioned with psychotic conditions such as schizophrenia or bipolar disorder may actually have a treatable immune disorder. According to a study published in the journal Lancet Psychiatry, antibodies attacking parts of the brain may be involved in up to one in every eleven cases of psychosis. According to new research, there is a link between psychosis and a genetic change that affects the immune system in the brain. The findings could have an impact on the development of modern medications for bipolar disorder or schizophrenia.

A new study from Sweden’s Karolinska Institutet suggests a link between psychosis and a genetic change that affects the brain’s immune system. The study, which was published in the journal Molecular Psychiatry, could have an impact on the development of modern medications for bipolar disorder or schizophrenia.

Psychosis affects about 2-3% of the population and is characterized by a shift in perception of reality, often accompanied by hallucinations and paranoid reactions. The majority of those affected have schizophrenia, but people with bipolar disorder may also experience psychotic symptoms. Antipsychotics available today frequently have insufficient efficacy, and patients’ lives can be difficult.

Our experimental data are confirmed by genetic studies in which we see a link between psychosis in bipolar disorder patients and decreased expression of GRK3, which leads to an increased amount of kynurenic acid in the brain.

Carl Sellgren

In the early 1980s, it was proposed that schizophrenia was caused by dysfunctional synapses, which are the places in the brain where nerve signals are transmitted. However, researchers could only study this indirectly, such as in postmortem brain samples or in lab animal and cell models. According to Sweden’s National Board of Health and Welfare, people with schizophrenia have a 15-year lower life expectancy than the general population.

“Although it is not entirely clear what biological mechanisms cause psychosis, recent research suggests that immune activation in the brain’s glial cells may be the culprit. People suffering from psychosis have higher levels of kynurenic acid in their brains, which is a messenger that sends information from the brain’s immune system to the neurons” Goran Engberg, Professor at Karolinska Institutet’s Department of Physiology and Pharmacology and the study’s corresponding author, agrees.

Previous genome-wide association studies (GWAS) have shown that the protein GRK3 expresses itself in patients with psychosis through genetic changes in the immune system.

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New findings linking brain immune system to psychosis

Researchers at Karolinska Institutet, the University of California, San Diego, and the Mayo Clinic in Rochester, Minnesota, have studied which parts of the immune system influence psychotic disorders in greater detail.

The study is based on extensive data from mice lacking the GRK3 protein in the brain, as well as a genome analysis of 70 people with bipolar disorder and 48 healthy control subjects. The loss of the GRK3 protein appears to increase immune system sensitivity and triggers a cascade of effects in the brain, including an increase in the release of the cytokine IL-1beta and kynurenic acid.

“Our experimental data are confirmed by genetic studies in which we see a link between psychosis in bipolar disorder patients and decreased expression of GRK3, which leads to an increased amount of kynurenic acid in the brain,” Carl Sellgren says. He is a senior lecturer at Karolinska Institutet’s Department of Physiology and Pharmacology and the study’s first author, along with Sophie Imbeault, a senior researcher in the same department.

The study’s findings establish a link between immune activation and psychosis, paving the way for further research into novel antipsychotic drugs with immune modulatory properties.

The drugs that are currently used to treat psychosis were developed in the 1960s. “More knowledge about the mechanisms in the brain that can trigger psychosis is needed to develop effective, modern drugs,” says Sophie Erhardt, professor at Karolinska Institutet’s Department of Physiology and Pharmacology and the study’s last author.

Because all of the people with schizophrenia who were scanned had received antipsychotic medication, the researchers wanted to rule out this as a factor in the synaptic dysfunction. They administered antipsychotic drugs, haloperidol and olanzapine, to rats for 28 days and discovered that they had no effect on SV2A protein levels.

According to Professor Howes: “This is reassuring because it suggests that our antipsychotic medications are not causing brain connection loss. Next, we hope to scan younger people in the very early stages of the illness to see how synaptic levels change as the illness progresses and whether these changes are established early on or develop over time.”

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