Two Genes Identified as Targets for Schizophrenia Treatment


Schizophrenia is a mental disorder whereby impaired brain development leads to imbalanced signals within the brain. Patients suffer from hallucinations, paranoia, and a decreased quality of life.

Two genes, DTNBP1 (Dystrobrevin Binding Protein 1) and BDNF (Brain-Derived Neurotrophic Factor), have been found to be new targets for treating schizophrenia. Researchers from Duke-NUS Graduate Medical School Singapore linked an underlying cause of schizophrenia with abnormal behaviour of these two genes.

As lowered DTNBP1 levels and genetic disruptions of DTNBP1 gene were associated with schizophrenia-like behaviour in mice, Assistant Professor Shawn Je and his team of scientists from the Neuroscience and Behavioural Disorder Programme at Duke-NUS, studied the signalling activity of cultured neurons that lacked the DTNBP1 gene or had lowered levels of this gene. They discovered that decreased levels of DTNBP1 resulted in interneurons not functioning normally and the neuronal network being over-activated. In addition, a decline in DTNBP1 reduced the levels of the secreted protein, BDNF.

Je shared that, “We wanted to understand the mechanism by which the brain circuit operates. 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.”

DTNBP1 provides a crucial transport mechanism that delivers BDNF to interneurons, and BDNF is important for the function of interneurons in brain circuitry. The absence of BDNF leads to abnormal circuit development and brain network activity as observed in schizophrenia patients. Importantly, Je and his team found that restoring BDNF levels in the brain resulted in normal brain development and activity, even though DTNBP1 was still absent.

This is a pioneer study showing the two genes, DTNBP1 and BDNF, function together, and how abnormal delivery of BDNF affects the brain network. Potential treatment could also be designed to enhance BDNF levels. Je and his team plan to test their findings in animal models.

The original research paper can be accessed here.

Source: Eureka Alert.