Schizophrenia Genes Unlock Treatment For Disorder

First Posted: Sep 21, 2015 05:38 PM EDT

Researchers at Duke-NUS Graduate Medical School Singapore (Duke-NUS) linked the abnormal genes (BDNF and DTNBP1) to underlying links of schizophrenia, a disabling brain disorder that's estimated to affect anywhere between 200,000 to 3 million in the United States annually. Symptoms of the health issue typically manifest during the teenage years or young adulthood, with problems ranging from paranormal behaviors to hallucinations.

"We wanted to understand the mechanism by which the brain circuit operates," explained senior author Assistant Professor Shawn Je, from the Neuroscience and Behavioural Disorders Programme at Duke-NUS, in a news release. "In particular, we wanted to understand the ability of a specific type of cell in the brain, termed interneurons, to modulate brain network activity to maintain a balance in brain signalling."

During the study, researchers analyzed signaling activity in neuronal cultures that either did not have the DTNBP1 gene or had lowered levels of the gene as a result of reduced DTNBP1 levels and genetic disruptions DTNBP1 in mice, resulting in schizophrenia-like behaviors.

With the help of model symptoms, researchers discovered low levels of DTNBP1 showed in dysfunctional interneurons and over-activated neuronal network activity, according to researchers. When DTNB1 levels were reduced, lowering the levels of the secreted protein molecule BDNF.

Researchers then found BDNF to be one of the most important factors that regulated the development of a normal brain circuit, playing an important role in the intreneurons ability to connect to the brain. Interneurons receive BDNF through a transport system that's run by DTNBP1 that's likened to the delivery of a parcel. Without BDNF, the abnormal circuit development and brain network activity observed in schizophrenia patients results.

While the two genes DTNBP1 and BDNF have been singled out as risk genes for schizophrenia in studies before, this study shows how the two function together, focusing on the importance of abnormal delivery of BDN. The study also sheds considerable insight on how the brain network develops, according to researchers, presenting further possibilities on treatments for the health issue based on BDNF levels. 

More information regarding the findings can be seen here

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