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New Genes Identified That Are Associated With ADHD

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During this innovative study, scientists led by Dr Matt Parker from Surrey set out to understand more about ADGRL3, a gene closely linked to ADHD and other ‘externalising’ disorders, in promoting behaviours such as substance abuse, which can be associated with the conditions. Through this work, scientists identified several new genes related to externalising disorders, which could lead to the development of new medication to lessen the impact on individuals.

Dr Matt Parker, Senior Lecturer in Neuroscience and Sleep Science at the University of Surrey, said:

“The high degree of heritability of externalising disorders, such as ADHD, has intensified the search to identify genes which cause such behaviours, which we hope will help develop targeted treatment options to alleviate their symptoms.

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“It is important we do this as not only will it help individuals better manage their condition, but it may also help improve their life chances - for example an estimated 26 percent of prison inmates have ADHD.”

Scientists used zebrafish as they share 70 percent of genes with humans –84 percent of these genes are known to be associated with human disease. Using a behavioural task which tracks the ability and willingness of the fish to ‘wait’ for a reward, scientists found zebrafish with the ADGRL3 gene-edited out had higher levels of inattention and demonstrated greater impulsivity when compared to wild-type fish with the normal functioning gene.  These characteristics were more prominent in male zebrafish lacking ADGRL3 compared to their female peers.

Treatment with atomoxetine, a medication used to treat ADHD, completely reversed the impulsivity.

Next the team studied genetic differences in the brains of zebrafish with and without the gene ADGRL3. They did this because ADGRL3 is a gene that is important in the development of the nervous system, so its dysfunction will have knock-on effects elsewhere. Interestingly, they found evidence supporting the idea that the immune system is crucial in the development of ADHD and similar disorders. They identified several genes and enriched gene clusters that were independent of drug treatment which may contribute to behaviours of those with externalising disorders.

Dr Parker added: 

“The discovery of these genes is very exciting as it demonstrates that there are more genes contributing to externalising disorders than we previously thought. Identification of such genes is potentially the first step in the development of new targeted medications to help patients better manage their symptoms.”

Reference: Fontana BD, Reichmann F, Tilley CA, et al. adgrl3.1-deficient zebrafish show noradrenaline-mediated externalizing behaviors, and altered expression of externalizing disorder-candidate genes, suggesting functional targets for treatment. Transl Psychiatry. 2023;13(1):304. doi: 10.1038/s41398-023-02601-4

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