Science

Two blood biomarkers of schizophrenia have been identified – Sciences et Avenir

According to the World Health Organization (WHO), schizophrenia affects “more than 23 million people around the world.” This psychiatric pathology is characterized by “an altered perception of reality, productive manifestations, such as delusions or hallucinations, and passive manifestations, such as social and relational isolation”, as Inserm details in his homonymous dossier.

Among patients suffering from this pathology, the symptoms are very heterogeneous, which does not help medical personnel to make a diagnosis. The identification of biomarkers, measurable characteristics in patients that can serve as “fingerprints” for certain diseases, would facilitate this step. Some have already been identified in the case of schizophrenia, for example an abnormally high level of hydrogen sulfide in the brain.

When conducting a translational study between animal models and human patients, a team of researchers from the University of Lausanne (Switzerland) recently identified two new measurable biomarkers of schizophrenia in the blood.

Parvalbumin neurons and mitochondria

The researchers focused their interest on a specific type of cell: parvalbumin neurons. More specifically, they studied the mitochondria of these neurons, organelles that are part of cells and are absolutely essential for their functioning as they are their source of energy.

Mitochondria, cell batteries:

To produce energy, many chemical reactions take place in the mitochondria. Some of them produce free radicals, very unstable molecules that run the risk of damaging other molecules making them unstable in turn. That is why they are normally evacuated very quickly outside the cells, through the so-called “antioxidant system”, to prevent the cells from suffering from “oxidative stress”.

Kim Q. Do, professor of neuroscience at the Center for Psychiatric Neurosciences (CNP) in Switzerland, explains that “the last decades of research have identified that a molecule of the antioxidant system, glutathione, is deficient in schizophrenic patients.” However, “its deficiency leads to an alteration of the parvalbumin neurons, a type of neuron directly involved in all the cognitive functions of the brain and, therefore, of thought”. It is one of the most persistent clinical manifestations in patients.

In these damaged neurons, particularly in the prefrontal cortex that plays a key role in processing emotions, dysfunctional mitochondria accumulate. Inès Khadimallah, researcher in Kim Do’s laboratory and first author of the study in question published in the journal Molecular Psychiatry, details that “normally, they are eliminated or recycled. Therefore, the cleaning system is probably no longer functional ”, which leads to a strong increase in oxidative stress.

Two key molecules for two categories of patients

In these cells subjected to strong oxidative stress, the researchers observed precisely two molecules, called miR137 and COX6A2 respectively. The former plays a central role in the famous cleansing system mentioned above, and the latter is the product of cellular respiration. In schizophrenic patients, the amount of miR137 is very high, a sign that the cleaning system is not sufficiently activated, while the level of COX6A2 is extremely low, indicating that cellular respiration is dysfunctional.

The levels of miR137 and COX6A2 can be measured in the blood of patients. Using these two molecules as biomarkers, the researchers found that two categories of schizophrenia patients emerged: with or without mitochondrial problems. Inès Khadimallah specifies that “patients suffering from a mitochondrial defect have more severe clinical symptoms than others”, with among other consequences a loss of autonomy and a decline in social skills.

In the case of a mitochondrial abnormality, the development of an antioxidant treatment, specifically targeting this dysregulation of brain mitochondria, would improve the condition of parvalbumin neurons and, ultimately, of patients. As Kim Q. Do summarizes, “Our work paves the way for an accurate diagnosis, as well as early and individualized treatment for those at high clinical risk.”

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