Scientists are getting closer to understanding the wiring in the brain that gives schizophrenia patients auditory hallucinations. A study in Nature Medicine says researchers from St. Jude Children’s Research Hospital, using mice, found a molecule linked to normal and abnormal function in the part of the brain where the hallucinations — like voices — originate. Specifically, the trouble comes when that molecule of microRNA is depleted.

RNA appears in the nucleus of a cell and above all else is a messenger molecule, carrying instructions from our DNA to others about which proteins they should produce. Thus microRNA is a small piece of the RNA that regulates how certain genes in our DNA are expressed, for instance helping to make them active or inactive.

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When the piece of microRNA in the brain that the researchers identified, called miR-338-3p, begins to disappear as a result of a genetic abnormality, the levels of a certain protein increase because it is no longer being regulated properly, the study says. And when that protein increases, it disrupts the flow of information between brain regions that process auditory information, so it can lead to hallucinations. In the brains where this imbalance occurs, children could behave abnormally and are later at a high risk for developing schizophrenia.

speak-238488_1920 A certain molecule in the brain may be the reason people with schizophrenia hear things that aren't really there — and targeting the molecule could cure their hallucinations. Image courtesy of Pixabay, public domain

Antipsychotic drugs have already been targeting this unregulated protein — it is a dopamine receptor, binding to the chemical that controls everything from our emotions to our motor function — but those drugs can have unpleasant side effects, corresponding author Dr. Stanislav Zakharenko noted in a statement from St. Jude. Targeting the microRNA that regulates the levels of this protein instead “could be targeted for development of a new class of antipsychotic drugs with fewer side effects.” The Nature Medicine study says replenishing the levels of miR-338-3p in mice did the job.

The molecule’s discovery also provides some insight into why schizophrenia and its associated hallucinations typically don’t appear in young children — it could be that the microRNA decreases over time and those symptoms only emerge once it falls below the minimum necessary to control the levels of the problem protein, St. Jude explains.

St. Jude’s team is studying brain disorders like schizophrenia, according to its statement, “to improve understanding of how normal brains develop, which provides insights into the origins of diseases like cancer.”

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Source: Zakharenko SS, Chun S, Du F, et al. Thalamic miR-338-3p mediates auditory thalamocortical disruption and its late onset in models of 22q11.2 microdeletion. Nature Medicine. 2016.