Inflammation enhances risk factors in schizophrenia.

Among all people, in their late teens, there is a natural thinning of the least desirable connections between neurons, the so-called synapses.

This process is important for the brain to develop in the best way. But people with schizophrenia have fewer synapses in the brain than people without the disease.

Researchers from Karolinska Institutet showed a few years ago that the breakdown of synapses in schizophrenia is increased. They also showed that this could be linked to a genetic risk variant for the disease and that it affects a specific protein, C4A.

High levels of protein in the disease

Now the same researchers have developed a method that enables them to measure protein levels in cerebrospinal fluid. In two groups of patients, the researchers could see that levels were elevated in patients who had recently had the first symptoms of psychosis, and who developed schizophrenia at later follow-up.

After controlling for an increasing number of genetic risk variants in patients, we still saw elevated levels of C4A, says PhD student Jessica Gracias-Lekinder at KI.

Cytokines move protein

On frequent occasions, two different cytokines, IL-1beta and IL-6, which are produced by the immune system during inflammation, have also been shown to be elevated in patients with schizophrenia.

So the researchers conducted further experiments showing that these cytokines stimulate the expression of the C4A protein. Patients with high levels of the protein also have particularly high levels of IL-1beta.

This suggests that the mechanism we see in the lab is also relevant to patients’ brains and that inflammation enhances the effect of a genetic risk variant, says Karl Silgren Magkowitz, a researcher at the Karolinska Institutet.

It can lead to more effective treatments

The researchers hope the findings will lead to more effective and targeted therapies for early-stage schizophrenia.

Currently available treatments are not individually tailored and focus on reducing symptoms for patients who already have the disease, says Karl Sejren Magkowitz.

Scientific study:

CSF concentration of complement component 4A is increased in the first episode of schizophreniaNature Communications.

Contact:

Carl Sellgren Majkowitz, Senior Physician and Researcher in the Department of Physiology and Pharmacology, Karolinska Institutet, [email protected]