Single Gene Mutation May Predispose to ADHD

Dr. Anders Nykjaer MD, PhD Mayo Clinic in Florida and Aarhus University in Interview with:
Dr. Anders Nykjaer MD, PhD
Mayo Clinic in Florida and
Aarhus University in Denmark

MedicalResearch: What are the main findings of the study?

Dr. Nykjaer: It is well known that ADHD is a complex condition caused by a number of factors including genetic and environment. However, approximately 75% etiology is considered to be genetic and a large body of investigations suggests that it is multiple genes each with a moderate effect that is responsible for conferring susceptibility to ADHD. We have here found one single gene the dysfunction of which is sufficient to trigger the disease.  The gene encodes a receptor, SorCS2, which ensures correct wiring our reward system during embryonic development. Malfunction of the receptor causes ADHD-like symptoms in mice. It is well accepted that ADHD predisposes to psychiatric disorders and genetic reports have linked variations in the SorCS2 gene with schizophrenia. Studies are currently ongoing to evaluate if mutations disrupting the function of SorCS2 may also result in schizophrenia. If this is the case we have come closer to an explanation for the link between ADHD and psychiatric disorders. In the future when prenatal genetic screening becomes established, non-sense mutations in the SorCS2 gene can be used to predict that the child will develop ADHD with 100% certainty.  

MedicalResearch: Were any of the findings unexpected?

Dr. Nykjaer: Yes, that a mutation in single gene is sufficient for development of ADHD. Moreover the function of the gene was completely unknown to us when we started the project. We suspected that SorCS2 is important in the brain. We just didn’t know what it was doing.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Nykjaer: With our study, we come a little closer to understanding the underlying causes of ADHD. Rather than just treating the symptoms of the disease as is done today, we can now start to think about how to reverse the potential miswiring in the brains of ADHD patients.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Nykjaer: Exactly the above. We need to increase the knowledge of how the connections in the brain are formed, maintained and even changed. Facilitating these processes by therapy may be a potential treatment for ADHD. Moreover, we need to understand whether mutations in SorCS2 may also result in schizophrenia. Genetic studies suggest this could be the case and if confirmed in animals models and large genetic screens it may explain the comorbidity of ADHD and schizophrenia.


SorCS2 Regulates Dopaminergic Wiring and Is Processed into an Apoptotic Two-Chain Receptor in Peripheral Glia

Glerup, Simon et al.

Neuron , Volume 82 , Issue 5 , 1074 – 1087



Last Updated on June 11, 2014 by Marie Benz MD FAAD