Researchers identify gene heavily linked to psychiatric disease

Brain diseases are hard to study because the brain is the most complex organ in the human body. However, researchers have now gotten further in understanding how one specific gene is involved in a range of mental illnesses.

“We have found a gene that seems to be heavily linked to psychiatric diseases such as schizophrenia, autism spectrum disorder, ADHD and epilepsy. We first identified the gene as a plausible link in big data for brain development, and then we went on to test whether this gene did drive the development of the disease using in two mouse models,” says senior author to the study, Konstantin Khodosevich of the Biotech Research and Innovation Centre (BRIC).

“Even though we obviously cannot measure symptoms of psychiatric disease in mice with the same precision as we can in humans, the results were quite convincing. The mice clearly showed signs of these psychiatric diseases such as difference in behavioral patterns, locomotion, anxiety, and confusion,” says Konstantin Khodosevich.

Algorithms found the genetic culprit

Before being able to test the functional changes caused by the gene, the researchers had to identify it. They knew from previous studies that a certain region of the human genome was associated with these psychiatric diseases. However, the region contained multiple genes that could explain the development of disease. In addition, it was actually proposed that two other genes than the one the researchers identified were responsible.

However, instead of doing sophisticated animal studies for each gene, they used a different approach. The researchers used an algorithm on available big data for brain development and investigated which of these genes were active.

“In all of the datasets, we saw that only this one gene in the region was active during development. This was of course very interesting to us since we know that these psychiatric diseases arise during development. So the genes responsible for the disease had to be active at this point in time,” says Konstantin Khodosevich.

“When we add up data on gene function in animal models together with the previously analyzed big data during brain development, we are quite convinced that the gene should have functional relevance to humans,” he adds.

New knowledge could help choosing the right treatment

The researchers also have an explanation for why this specific gene may be involved in the psychiatric diseases.

“We know that this gene regulates many other genes. We think that it changes or inhibits the proliferation and maturation of stem cells. This means that not enough stem cells mature to become nerve cells in our brain, which could explain the link between the gene and mental illness,” explains Konstantin Khodosevich.

The researchers do not think that this particular gene can be used as a target for medicine or genetic editing. However, they do underline that this new knowledge could be important to have for health professionals in the future in order to choose the right treatment as many different genetic mutations could lead to the same diseases or symptoms.

They will also now take the same approach to identify more genes involved in psychiatric and other disorders of brain development.

Read the entire study in Biological Psychiatry: “Identification of vulnerable interneuron subtypes in 15q13.3 microdeletion syndrome using single-cell transcriptomics”

The research was supported by the Lundbeck Foundation and the Novo Nordisk Foundation.

Contact

Associate Professor Konstantin Khodosevich
+45 35 33 25 33
konstantin.khodosevich@bric.ku.dk

Press Officer Mathias Traczyk
93 56 58 35
mathias.traczyk@sund.ku.dk