Scientists may have found a way to make the 'voices in the head' heard by some people with schizophrenia appear quieter. A team of researchers has learnt more about the molecular mechanisms that can lead people to have hallucinations and "hear voices". The findings may also explain why psychotic symptoms of schizophrenia often only appear late, in adolescence or early adulthood.
The scientists worked with mice models of the 22q11 deletion syndrome – these animals are missing part of chromosome 22. Humans who suffer from this syndrome have a greater risk of having behaviour problems as children; between 23 and 43% go on to develop schizophrenia, with symptoms such as hallucinations.
In the mice with 22q11 deletion syndrome, the neural circuit connecting two brain regions involved in auditory hallucinations had in the past been found to be specifically disrupted. However, scientists did not really understand how and why it was disrupted.
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In this research, published in Nature Medicine, they have identified a microRNA (see box) known as miR-338-3p as a potential factor of this disruption.
What are microRNAs?
RNA is an important molecule with long chains of nucleotides - the name stands for "ribonucleic acid". RNA's role is to transfer the genetic code needed for the creation of proteins from the nucleus to the ribosome in the cell. The process helps the DNA and genetic code to be protected from damage. Without RNA, proteins could not be synthesised.
In the body, there are more than 2,000 microRNAs – small RNA fragments – whose function is to silence expression of particular genes and regulate the supply of the corresponding proteins.
Levels of miR-338-3p were lower in the thalamus of individuals with schizophrenia compared to individuals of the same age and sex without the diagnosis. This was linked to reduced signalling in the circuit that links the thalamus and auditory cortex, which is implicated in the formation of auditory hallucinations. When the scientists replenished levels of the microRNA in the auditory thalamus of the mice, this restored the circuit to normal functioning.
The scientists also found clues to explain why it is adults and not children that tend to "hear voices". Researchers observed that microRNA levels declined with age in mice, whether they suffer from deletion syndrome or not. For those that do, this can be very problematic.
"While miR-338-3p levels decline as normal mice age, levels may remain above the threshold necessary to prevent over-expression of the protein and hallucinations. In contrast, the deletion syndrome may leave mice at risk for dropping below that threshold," corresponding author Stanislav Zakharenko, from St Jude Department of Developmental Neurobiology said.
The scientists suggest that the role of the microRNA could be further studied and that it may become the target of a new class of antipsychotic drugs with fewer side effects than the ones currently available.