Scientists have been able to link the abnormal behaviour of two genes to the underlying cause of schizophrenia. The findings provide a new target for schizophrenia treatment.
The major cause of the devastating mental disorder -- that affects nearly one percent of the total human population -- lies in impaired brain development that eventually leads to imbalanced signals within the brain.
This imbalance within the brain is thought to cause hallucinations and paranoia in people with schizophrenia.
"We wanted to understand the mechanism by which the brain circuit operates," said senior study author Shawn Je from Duke-NUS Graduate Medical School Singapore.
Je and his team analysed signalling activity in neuronal cultures that either did not have a gene called DTNBP1 or had low levels of it.
Reduced DTNBP1 levels and genetic disruptions of DTNBP1 in mice resulted in schizophrenia-like behaviours.
Using multiple model systems, they found that the low levels of DTNBP1 resulted in dysfunctional interneurons and over-activated neuronal network activity.
Reducing levels of DTNBP1 also lowered the levels of the secreted protein molecule, BDNF.
BDNF was then shown to be one of the most important factors that regulate the development of a normal brain circuit.
Additionally, Je and his 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 study not only singled out the two genes -- DTNBP1 and BDNF -- as risk genes for schizophrenia, it also showed that the two function together.
