Discovery of a common genetic link between autism and Tourette’s disease – Altered brain communication

This is an MRI of the brain. Credit: Lancaster University

Researchers at Lancaster University have discovered, for the first time, how a genetic alteration that increases the risk of developing autism and Tourette’s effects on the brain.

Their research also suggests that ketamine, or related drugs, may be a useful treatment for both disorders.

Autism affects around 2.8 million people in the UK, while Tourette’s syndrome – a condition that causes a person to make involuntary sounds and movements called tics – affects around 300,000 people in the UK. The treatments available for both disorders are limited and new treatments are urgently needed. Recent research has also shown that these disorders are genetically linked.

People with a genetic deletion known as a chromosome 2p16.3 deletion often have developmental delay and learning difficulties. They are also around 15 times more likely to develop autism and 20 times more likely to develop Tourette syndrome, but the mechanisms involved are not fully understood.

Using brain imaging studies, neuroscientists have shown that deletion of the gene impacted by deletion of 2p16.3 (Neurexin1) impacts the function of brain regions involved in both conditions. A key finding is that this genetic deletion disrupts an area of ​​the brain known as the thalamus, compromising its ability to communicate with other areas of the brain.

Lead researcher Dr Neil Dawson of Lancaster University said: “We currently have a very poor understanding of how deletion of 2p16.3 dramatically increases the risk of developing these disorders.

However, we do know that the 2p16.3 deletion involves the deletion of the Neurexin1 gene, a gene that makes a protein responsible for allowing neurons to communicate effectively.

The deletion of the Neurexin1 gene affects brain areas implicated in autism and Tourette’s disease, including the thalamus, a set of brain regions that play a key role in helping other brain areas communicate with each other. Changes were also found in brain regions involved in processing sensory information and in learning and memory.

Importantly, the researchers also found that the ability of thalamic brain regions to communicate with other brain regions was altered by the genetic deletion. They then tested the ability of a low dose of the drug ketamine, a drug used clinically in higher doses as an anesthetic, to normalize the alterations in brain function induced by the gene deletion.

Dr Dawson said: “Curiously, our data suggest that ketamine may restore some aspects of brain dysfunction resulting from 2p16.3 deletion and suggest that ketamine, or other related drugs, may be useful in the treatment of some of the symptoms seen in autism and Tourette’s The affected brain circuits suggest that these drugs may be particularly useful for the cognitive and motor problems experienced by people with these disorders.

Interestingly, ketamine has been shown to normalize activity in thalamic regions found to be overactive as a result of genetic deletion and restore these regions’ ability to communicate with other areas of the brain. This suggests that ketamine, or related drugs, may be a useful treatment for people with 2p16.3 deletion or with autism and Tourette’s syndrome, although more research is needed.

Dr. Dawson urges caution for those considering using ketamine for therapeutic purposes.

“While these data give us important new insights into the brain circuitry affected by the 2p16.3 deletion and the potential utility of ketamine in helping people with autism and Tourette’s, much more research needs to be conducted. to prove its clinical potential. We know that ketamine impacts the activity of several regions of the brain in addition to the thalamus, and effects in these other regions are likely to cause undesirable side effects. Long-term use of ketamine may have negative consequences that are not yet fully understood.We also believe that ketamine may not be the best treatment option due to its relatively short lifespan in the body.

“However, the results of this study give us important clues regarding the types of drugs that may be useful in the treatment of these disorders, and we are using this information to actively pursue the validation of these drugs for the potential treatment of these disorders. ”

Reference: “Ketamine Restores Thalamic-Prefrontal Cortex Functional Connectivity in a Mouse Model of Neurodevelopmental Disorder-Associated 2p16.3 Deletion” by Rebecca B Hughes, Jayde Whittingham-Dowd, Rachel E Simmons, Steven J Clapcote, Susan J Broughton and Neil Dawson, December 8, 2019, Cerebral cortex.
DOI: 10.1093/cercor/bhz244

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