Researchers at Lancaster University have been the first to discover a genetic alteration that increases the risk of developing Autism Spectrum Disorder and Tourette Syndrome, as published in the journal Cerebral Cortex. Their findings suggest that ketamine, or related drugs, may be a useful treatment for both disorders.

Autism Spectrum Disorder (ASD) is a developmental disorder characterised by difficulties with communication and social interaction, affecting ~2.8 million people in the UK. Tourette Syndrome is a nervous system disorder characterised by involuntary movement and sounds known as tics, affecting ~300,000 people in the UK.

Treatments for both disorders are limited, and new approaches are urgently required. Previous studies have suggested that NMDA receptors may be a potential therapeutic target for these disorders.

A known genetic deletion, chromosome 2p16.3, is linked to an increased susceptibility to ASD, schizophrenia, developmental delay, and intellectual disability – with a highly variable phenotype and incomplete penetrance. It’s involved in exons of the Neurexin1 (NRXN1) gene, playing a role in synaptic neurotransmission. People with this deletion are ~15 times more likely to develop ASD and ~20 times more likely to develop Tourette’s Syndrome, but the mechanisms involved are not completely understood.

The researchers investigated the ability of ketamine, a NMDA-receptor antagonist, at low doses. Clinically, the drug is used at higher doses as an anaesthetic.

The study was carried out on 2p16.3 heterozygous deletion mice models to characterise cerebral metabolism and their functional brain network connectivity. Neuroscientists showed that the deletion impacts the functions of brain regions involved in both conditions. The brain image studies revealed that the thalamus is compromised in its ability to communicate with other brain regions, and changes were also found in brain regions involved in processing sensory information and in learning and memory.

The results suggested that ketamine, or other related drugs, can be used to restore some aspects of brain dysfunction in 2p16.3 individuals. The brain circuits affected in these disorders suggest that these types of drugs may be particularly useful to treat the cognitive and motor problems present in these disorders. Ketamine seemed to re-establish the ability of these regions to communicate with other brain areas.

Further research needs to be carried out with ketamine and related drugs to full determine how helpful it is to people with ASD and Tourette’s. The researchers urge caution to those who may be thinking of using ketamine therapeutically. Side-effects of the drug are not fully understood, and long-term ketamine treatment could have negative consequences.

Even so, this study provides a basis in understanding what types of drugs may be useful therapeutically, and the team are continuing to seek the validity of these drugs as a potential treatment for Autism and Tourette’s.