Scientists dig deeper into the genetics of schizophrenia by evaluating microRNAs

Joseph A. Gogos, M.D., Ph.D. associate professor of physiology and neuroscience, Columbia University Medical Center Click here for more information.

NEW YORK – Researchers at Columbia University Medical Center have illuminated a window into how abnormalities in microRNAs, a family of molecules that regulate expression of numerous genes, may contribute to the behavioral and neuronal deficits associated with schizophrenia and possibly other brain disorders.

In the May 11 issue of Nature Genetics, Maria Karayiorgou, M.D., professor of psychiatry, and Joseph A. Gogos, M.D., Ph.D., associate professor of physiology and neuroscience at Columbia University Medical Center explain how they uncovered a previously unknown alteration in the production of microRNAs of a mouse modeled to have the same chromosome 22q11.2 deletions previously identified in humans with schizophrenia.

“We’ve known for some time that individuals with 22q11.2 microdeletions are at high risk of developing schizophrenia,” said Karayiorgou, who was instrumental in identifying deletions of 22q11.2 as a primary risk factor for schizophrenia in humans several years earlier. “By digging further into this chromosome, we have been able to see at the gene expression level that abnormalities in microRNAs can be linked to the behavioral and cognitive deficits associated with the disease.”

The investigators modeled mice to have the same genetic deletion as the one observed in some individuals with schizophrenia and examined what happens in the expression of over 30,000 genes in specific areas of the brain. When they discovered that the gene family of microRNAs was affected, they suspected that the Dgcr8 gene was responsible. The Dgcr8 gene is one of the 27 included in the 22q11.2 microdeletion and has a critical role in microRNA production, so this was a logical hypothesis. Indeed, when they produced a mouse deficient for the Dgcr8 gene, and tested it on a variety of cognitive, behavioral and neuroanatomical tests, they observed the same deficits often observed in people with schizophrenia.