Schizophrenia affects nearly 1% of the total human population. The major cause of the devastating mental disorder lies in impaired brain development that eventually leads to imbalanced signals within the brain. This imbalance is thought to cause hallucinations and paranoia. Now, researchers have been able to link the abnormal behavior of two genes to the underlying cause of schizophrenia. The findings provide a new target for schizophrenia treatment.
Senior study author Shawn Je from Duke-NUS Graduate Medical School Singapore said, "We wanted to understand the mechanism by which the brain circuit operates." The researchers analyzed signalling activity in neuronal cultures that either did not have a gene called DTNBP1 or had low levels of it.
Mice studies revealed that reduced DTNBP1 levels and genetic disruptions of DTNBP1 resulted in schizophrenia-like behaviors. Using multiple model systems, the research team found that the low levels of DTNBP1 resulted in dysfunctional interneurons and over-activated neuronal network activity. Reducing levels of DTNBP1 was also found to lower the levels of the secreted protein molecule, BDNF, that regulates the development of a normal brain circuit.
Additionally, the research team also found that when BDNF levels were restored, brain development and activity were rescued and returned to more normal levels, despite the absence of DTNBP1.
The findings of the study not only singled out the two genes, DTNBP1 and BDNF, as risk genes for schizophrenia, but it also showed that the two function together.