Skip to content

Study implicates two genes in the cause of schizophrenia, vital for signalling balance.

In the mammalian central nervous system, neurons receive inhibitory synaptic inputs from gamma-aminobutyric acid (GABA)ergic interneurons and excitatory inputs from glutamatergic neurons. Evidence suggests that the dysfunction of appropriate GABAergic inhibition and the consequent imbalance between excitation and inhibition in the cerebral cortex underlie the cause of schizophrenia.

Now, a study from researchers at Duke-NUS Graduate Medical School Singapore (Duke-NUS) has linked the abnormal behaviour of two genes (BDNF and DTNBP1) to the underlying cause of schizophrenia. The team state that these findings have provided a new target for schizophrenia treatment.  The opensource study is published in the journal Biological Psychiatry.

Previous studies show that Schizophrenia is a devastating mental disorder that affects nearly 1% of the total human population. The dominant cause of the disorder 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.  The lab state that while the two genes DTNBP1 and BDNF have been singled out as risk genes for schizophrenia in studies before, theirs is the first study to show that the two function together. They go on to add that pinpointing the importance of the abnormal delivery of BDNF has shed considerable insight into how the brain network develops; and presents possibilities for potential treatments for schizophrenia designed around enhancing BDNF levels.

The current study analysed signalling activity in neuronal cultures that either did not have the DTNBP1 gene or had lowered levels of the gene, because reduced DTNBP1 levels and genetic disruptions of DTNBP1 in mice resulted in schizophrenia-like behaviours. Results showed that the low levels of DTNBP1 resulted in dysfunctional interneurons and over-activated neuronal network activity. Data findings also showed that reducing levels of DTNBP1 lowered the levels of the secreted protein molecule, BDNF.

The team explain that they have shown that BDNF is one of the most important factors that regulate the development of a normal brain circuit. It plays an important role in the interneurons ability to connect to the brain with interneurons receiving BDNF via a transport system run by DTNBP1. The lab conclude that without BDNF, the abnormal circuit development and brain network activity observed in schizophrenia patients results.

The researchers surmise their findings show that when BDNF levels were restored, brain development and activity were rescued and returned to more normal levels, despite the absence of DTNBP1.  For the future the team plans to test if these findings are viable in an animal model, if so, this could mean that correcting the imbalance within the brain circuits of schizophrenia patients may bring the global medical communtiy closer to producing a treatment.

Source: Duke-NUS Graduate Medical School Singapore

 

This is an image of a cultured neuron with an added BDNF protein.  Credit:  Duke-NUS Graduate Medical School Singapore.
This is an image of a cultured neuron with an added BDNF protein. Credit: Duke-NUS Graduate Medical School Singapore.

Healthinnovations View All

Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.

Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.

Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.

Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.

Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.

An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.