New research at Karolinska Institutet in Sweden suggests a link between psychosis and a genetic change that affects the brain’s immune system. The study published in Molecular psychiatry may impact the development of modern drugs for bipolar disorder or schizophrenia.
Psychosis affects about 2 to 3% of the population and is characterized by a change in the perception of reality, often accompanied by hallucinations and paranoid reactions.
Most of those affected are patients with schizophrenia, but people with bipolar disorder may also experience psychotic symptoms.
The antipsychotics available today are often insufficiently effective, and for patients, their living situation can be difficult.
The average life expectancy of people with schizophrenia is around 15 years shorter than that of the general population, according to the Swedish National Board of Health and Welfare.
“It’s not entirely clear what biological mechanisms cause psychosis, but recent research suggests that immune activation in glial brain cells may be the cause. People with psychosis have high levels of kynurenic acid in the brain, a messenger that transmits information from the brain. immune system to neurons, ”says Goran Engberg, professor in the Department of Physiology and Pharmacology, Karolinska Institutet, and the corresponding author of the study.
Previous genome-wide association studies (GWAS) have shown that the GRK3 protein is expressed through genetic changes in the immune system in patients with psychosis.
Now, researchers at the Karolinska Institutet, University of California, San Diego, United States, and Mayo Clinic, Rochester, United States, have studied more specifically which parts of the immune system impact on psychotic disorders.
The study is based on extensive data from mice lacking the GRK3 protein in the brain, as well as genome analysis of 70 people with bipolar disorder and 48 healthy control subjects.
The results show that the loss of the GRK3 protein appears to increase the sensitivity of the immune system and trigger a cascade of effects in the brain, involving an increased release of the cytokine IL-1beta and kynurenic acid.
“Our experimental data is confirmed by genetic studies where we see a link between psychosis in patients with bipolar disorder and a decrease in the expression of GRK3, which leads to an increase in the amount of kynurenic acid in the brain, ”explains Carl Sellgren. He is a lecturer in the Department of Physiology and Pharmacology of the Karolinska Institute and first author of the study with Sophie Imbeault, senior researcher in the same department.
The study data establishes a link between immune activation and psychosis and thus presents a starting point for further study of new antipsychotic drugs with immunomodulatory functions.
The drugs currently used in the treatment of psychosis were developed in the 1960s.
“To develop effective and modern drugs, more knowledge is needed about the brain mechanisms that can trigger psychosis,” says Sophie Erhardt, professor in the Department of Physiology and Pharmacology at the Karolinska Institute and the latest author of the study.
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