The systematic review of scientific studies suggests that these molecules may provide a new diagnostic tool for the disorder in the future.

The study is the first comprehensive analysis to combine data from research on both blood and brain tissue samples. Despite the variation in data and methodology between studies, the findings were "surprisingly consistent," the researchers report.

"This is the first such comprehensive analysis combining the results of research conducted on both blood and brain tissue samples. The conclusions are surprisingly consistent — despite the scattered data and methodological differences between publications," the Wrocław Medical University press release says.

MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene activity without directly producing proteins.

According to the researchers: "They act as silencers: they mute the expression of specific genes, influencing the functioning of entire biochemical pathways. They are extremely sensitive to environmental factors, stress, infections, and diet, which is why they are considered potential carriers of information about the condition of the body and even the mind.”

In their review, the authors analyzed 77 scientific studies, which identified 124 microRNAs with altered expression in individuals with schizophrenia spectrum disorders. Some of these molecules showed abnormalities in both blood and brain samples. The researchers say that this is significant, as it indicates that pathological changes can potentially be detected from readily available blood samples, without the need for invasive brain tissue collection.

"This is important information because it indicates that it is possible to detect pathological changes in readily available samples, without having to sample brain material," the press release says.

The most consistent findings in the analysis concerned two particular microRNAs: miR-181b-5p and miR-34a-5p. Both were found to have elevated levels in individuals diagnosed with schizophrenia in 8 out of 10 studies analyzed.

"For both molecules, consistent expression changes were most frequently demonstrated in both the brain and peripheral blood, suggesting their potential diagnostic usefulness," said Marek Kotas, PhD, from the Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences.

The team employed AUC (Area Under the Curve) analysis, a statistical measure of diagnostic accuracy. For the selected microRNAs, the AUC index reached 0.98, which suggests that these molecules can be highly effective at distinguishing between individuals with schizophrenia and healthy controls.

"This gives hope that in the future, microRNAs could serve as psychiatric biomarkers, i.e., tools supporting diagnosis, assessing disease progression, and predicting treatment response. Moreover, these molecules can be measured in a standard blood sample," the press release says.

However, Kotas says there is a need for large, independent studies to validate these biomarkers. "Both to verify their sensitivity and specificity, and to determine the range of normal values," he said. Without such studies, miRNA expression would not be useful in clinical practice.

Kotas also highlighted the financial challenges of implementing miRNA-based testing, as the measurement of miRNA expression requires advanced and costly molecular techniques that are not currently part of routine diagnostic tests.

In addition to their potential role in diagnosing schizophrenia, the microRNAs in question may also have implications in cancer research.

"The reports of a reduced incidence of central nervous system tumors in people with schizophrenia are interesting," said Professor Błażej Misiak, Head of the Department and Clinic of Psychiatry at the Medical University of Warsaw.

Misiak noted that overexpression of miR-181b-5p and miR-34a-5p has typically been associated with anti-cancer effects. "Although more detailed studies are needed, it appears that there may be a link between the overexpression of these miRNAs and a lower risk of gliomas, perhaps through mechanisms promoting neuronal or glial cell death. However, this remains largely speculative for now," Misiak added. (PAP)

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