Scientists have identified a rare genetic mutation linked to schizophrenia.
After studying family members with a high rate of mental illness, researchers from Johns Hopkins University believe that a mutation in the gene Neuronal PAS domain protein 3 (NPAS3) is somehow tied to the development of mental illnesses such as schizophrenia.
It is known that NPAS3 is responsible for making sure that healthy neurons are consistently developed, especially in the hippocampus — an area of the brain affected in schizophrenia.
An abnormal mutation of this gene was discovered among certain members of a single family — the mutation caused NPAS3 to function incorrectly, which was detrimental to brain development.
The researchers believe that studying the biological role of NPAS3 will shed light on how other genes may also be responsible for mental illnesses like schizophrenia.
“Understanding the molecular and biological pathways of schizophrenia is a powerful way to advance the development of treatments that have fewer side effects and work better than the treatments now available. We could definitely use better medicines,” said lead author Frederick C. Nucifora Jr., Ph.D., D.O., M.H.S.
The researchers collected and analyzed blood samples from 34 patients with schizophrenia or schizoaffective disorder in order to study their DNA. Each participant came from a family with a history of mental illness. The scientists focused on seeking out people with a NPAS3 mutation.
They ended up finding one person and conducted blood tests on members of that family, including two parents and four adult children.
The findings revealed that the mother who has schizophrenia, as well as her two children with the same disorder and another suffering from depression, all shared the same mutant genetic variation of NPAS3.
In an effort to see if this specific mutation had any effect on the way NPAS3 should normally function, the researchers conducted another experiment. The scientists grew neurons with both mutated and normal versions of the gene in a dish and watched for any significant differences.
They discovered that the normal version of the gene has very long extensions which allow it to make good neuronal connections with other cells, while the mutated version has much shorter extensions in comparison.
“We showed that the mutation does change the function of NPAS3, with potentially harmful effects in neurons. The next step is to figure out exactly how the genetic disruption alters neuronal function, and how these abnormal neurons influence the broader function of the brain,” said Nucifora.
The report is published in the journal Molecular Psychiatry
Source: Molecular Psychiatry