Neurology Central

New genetic risk factor for schizophrenia identified

A small study at the Icahn School of Medicine at Mount Sinai (NY, USA) has revealed that microRNAs may be underexpressed in the brains of schizophrenia patients. The findings, which were published recently in Cell Reports, highlight another potential risk factor for the disease.

The research team, led by Kristen Brennand and Gang Fang (both Icahn School of Medicine), pioneered a new methodological approach in order to avoid the problems associated with investigating schizophrenia through the use of often hard-to-come-by live brain tissue. Researchers collected skin samples from each of the patients, reprogrammed the cells to form induced pluripotent stem cells and then differentiated these cells into precise subtypes of human neurons.

Specifically, they discovered that the microRNA, termed miR-9, was the most significantly underexpressed in a small group of 14 schizophrenic patients, when compared to six control participants. Further investigation of an additional 10 childhood-onset schizophrenic patients and 10 controls replicated these results.

Kristen Brennand commented: “Schizophrenia is a very complex disorder that is believed to be strongly genetically influenced – there are probably more than 1000 genes contributing to its development, some or many of which will affect individual patients.”

The team discovered that the genes controlled by miR-9 play a key role in the fetal development of neurons and in neural migration. The underexpression of genes therefore resulted in ‘miswiring’ of the brain.

miR-9 only represents the second identified microRNA associated with schizophrenia, however the team believe that there is likely many others. Interestingly, investigation of the genetic origins of schizophrenia has predominantly highlighted genes that are expressed during fetal development, despite the disorder only becoming symptomatic during adulthood.

“This is a heritable disease that runs in families, and it’s no one’s fault that someone was born with this genetic risk,” remarked Brennand.

The results of the recent study help to further validate the teams’ findings from a previous study published in JAMA Psychiatry earlier this year in which a genetic screen from 35,000 schizophrenia patients identified either low expression or mutation in the gene controlled by miR-9.

“The goal of our research is… ultimately to develop a screening platform that we can use to identify new therapeutics for the treatment of this debilitating disorder,” highlighted Brennand. “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.”

Source: Mount Sinai School of Medicine press release via EurekAlert!; Topol A et al. Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells. Cell Reports, (2016).