The exact biological mechanisms behind psychosis, a condition that changes one’s perception of reality and often involves paranoia and hallucinations, are largely unknown. Now, however, researchers have found a link between psychosis and a genetic change in the brain’s immune system.
"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," says Goran Engberg, one of the authors of the study.
Previous research has found that the protein GRK3 expresses itself via genetic changes in the immune system in patients with psychosis. As such, for the present study, the researchers decided to analyze data from mice investigating the GRK3 protein in their brains alongside genomes of 70 people with bipolar disorder and 48 healthy controls.
From their results, they found that loss of the GRK3 protein seems to lead to an increase in immune system sensitivity. This increases the release of cytokine IL-1beta, which induces the kynurenine pathway, something that has also been shown to occur in patients with schizophrenia or bipolar disorder from analyses of their cerebrospinal fluid.
The researchers also found that loss of the GRK3 protein induced hyper-responsiveness to D-amphetamine, which then elevated spontaneous firing of midbrain dopamine neurons. The researchers noted that such dysfunctional dopamine neurotransmission is also observed in many imaging studies of people with schizophrenia.
All in all, the researchers say that their analyses show that GRK3 deficiency induces the kynurenine pathway to signal inflammatory processes in neuronal circuits in the brain. They further say that, as similar processes have been found in both humans and mice, mice may provide a suitable animal model for translational studies of novel immunomodulatory agents to treat psychotic syndromes.