The discovery of a link between the abnormal behavior of a pair of genes and schizophrenia has suggested a new target for treatment of the mental disorder, researchers say.
In schizophrenia, which affects almost one percent of the global population, impairment in brain development can lead to an imbalance of signals inside the brain, often resulting in hallucinations and paranoia in its sufferers.
"We wanted to understand the mechanism by which the brain circuit operates," explains senior study author Shawn Je in the Neuroscience and Behavioral Disorders Program at Duke-NUS Singapore. "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 signaling."
The researchers focused on the gene DTNBP1, which has been shown to create schizophrenia-like behaviors in mice when it is below normal levels or has been subject to genetic disruption.
Reduced levels of DTNBP1 resulted in poorly-functioning interneurons and excessive neuronal network activity, and in turn also lowered the levels of another gene, BDNF, known to be an important factor in regulating normal brain circuit development, the researchers report in the journal Biological Psychiatry.
When they restored BDNF levels, the researchers found that brain development and neuronal activity were recovered and brought back to more normal levels, even with the low levels of DTNBP1.
Although previous studies have identified both DTNBP1 and BDNF as genes being involved in the risk of developing schizophrenia, the researchers claim that their work is the first to demonstrate how the function of two genes is interrelated.
The findings could lead to potential treatments based on enhancing BDNF levels, which could correct the imbalance in the brain circuits of schizophrenia sufferers.
The Duke-NUS medical school was created in 2005 as a partnership between Duke University in the U.S. and the National University of Singapore, with a curriculum based on that of the Duke University School of Medicine.
