The Key To The Development of Schizophrenia May Lay In MicroRNA

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Past research has strongly indicated that genetics plays a large role in the development of schizophrenia, but a new study shows the root of the mental disorder may be even deeper. According to a report published in the journal Cell Reports, microRNAs – extremely small molecules which play a role in gene expression – are largely under-expressed in individuals with schizophrenia.

In particular, a specific microRNA known as miR-9, which controls the activity of hundreds of genes, was found to play a key role in determining risk for the disease.

In the small pilot study, the researchers from Icahn School of Medicine at Mount Sinai found that miR-9 was notably under-expressed in cells of four schizophrenic patients when compared to six healthy control participants. The findings were then replicated in a larger sample of ten childhood-onset schizophrenic patients and ten control participants.

“Schizophrenia is a very complex disorder that is believed to be strongly genetically influenced — there are probably more than 1,000 genes contributing to its development, some or many of which will affect individual patients,” said lead co-author Kristen Brennand, Ph.D., Assistant Professor of Psychiatry at Mount Sinai.

“The better we are able to fill in the pieces to this very difficult puzzle, the more we can think about treatment, and, better yet, prevention.

According to the researchers, the genes controlled by miR-9 are a vital part of the fetal development of neurons and help set where neurons will eventually settle in the brain. If the miR-9 molecules are under-expressed, these genes may be less active than normal which may cause the brain to be miswired.

The findings are particularly notable because it may one day lead to a way to detect schizophrenia years before it appears. The research suggests the genes linked to the development of schizophrenia are expressed during fetal development while schizophrenia typically does not show itself until adulthood.

“The idea that children are born with schizophrenia should take the pressure off of parents,” said Brennand. “This is a heritable disease that runs in families, and it’s no one’s fault that someone was born with this genetic risk.”

The team notes that studying schizophrenia on a biological level can be difficult as there is little live brain tissue available for study. Instead, the researchers created a new approach that uses expertise in stem cell biology, neurobiology, genomics, and systems biology. In this method, they take skin samples from patients before reprogramming them into induced pluripotent stem cells. The stem cells can then be differentiated into precise subtypes of human neurons.

“The goal of our research is to not just understand the genetic mechanisms contributing to schizophrenia, but ultimately to develop a screening platform that we can use to identify new therapeutics for the treatment of this debilitating disorder.”

While the team eventually pinpointed miR-9 as the key molecule in this process, they also observed that numerous other microRNA to be differentially expressed in cells of those with schizophrenia.

“In fact, tens of miRNAs reached statistical significance and we wanted to identify a smaller number of key players,” said lead co-author Gang Fang Ph.D., and Assistant Professor in the Department of Genetics and Genomic Sciences.

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