ADHD, or attention deficit and hyperactivity disorder, is a common neurodevelopmental disorder with manifestation usually occurring in childhood. According to various sources, this condition affects from 3% to 30% of the population. Children with ADHD are easily distracted, hyperactive and impulsive. ADHD patients may be aggressive and have higher risks for the substance abuse and development of other mental disorders. Only 40% show improvement with age. The pathological mechanisms behind ADHD are still unknown, but scientists prefer the version of joint influence of genetic factors and environmental adversities (e.g., stress or illness of the mother during pregnancy, complications during labor, or diseases suffered in early childhood). The disorder has a complex genetic nature that hasn’t been addressed until recently. A team from I.M. Sechenov First Moscow State Medical University, together with foreign colleagues analyzed the genomes of several families that have members with ADHD.
Genotyping was conducted for 37 family members. The results have shown that all patients had specific features in certain genes. The identification of such patterns may help diagnose the condition itself in wide advance. The scientists focused on studying the rare functional variants in whole set of genes in several generations of families with running ADHD. They managed to follow the patterns for certain genes, e.g., AAED1. The protein produced by this gene binds with several other proteins that participate in dopaminergic and glutamatergic transmission. By itself, AAED1 is a gene belonging to antioxidant enzymes family and is known only very recently in the context of oncology. It is, indeed, able to regulate glucose utilization in cells (glycolysis) and the response to low oxygen environment (hypoxia), by interacting with the HIF-1 nuclear factor. Changes in its activity can potentially influence the excitability of some structures of the central nervous system leading to behavioral alterations.
Moreover, to the association with ADHD was discovered for another gene with a poorly understood function – ATAD2. It is a nuclear protein which interacts with certain regions in chromatin, regulating gene expression. Notably, these rare variants were also found in ADHD patients outside the studied families. These findings give further evidence for considering them as ADHD risk genes. The fact that both genes are involved in a potentially cascade picture (oxidative stress protection and gene regulation), paves the hypothesis that ADHD could be inserted in the whole picture of current thoughts on certain neurodegenerative diseases. More and more data are piling up concerning the role of DNA damage in neurons (e.g. induced right from oxidative stress), as potential trigger for psychiatric and neurologic diseases. Among these Parkinson disease, Huntington disease, ataxia teleangectasia (ATM) and autism-related syndromes.
Evgeniy Svirin, junior research associate of the laboratory of psychiatric neurobiology at I.M. Sechenov First Moscow State Medical University, explains: “We believe the development of ADHD may be caused by alterations in the structure of genes encoding proteins which participate in signal transmission in the nervous system using special biologically active substances – neurotransmitters. In the case of ADHD, the changes affect, among others, serotonin and dopamine pathways in the nervous system that play an important role in the processes of attention, motivation, and learning. We have discovered new rare functional variants associated with the risk of ADHD development. Our results may be of use for the development of genetic diagnostics methods for this complex disorder. Further studies of the rare AAED1 gene variant on brain development, that are already carried out by our joint team with German researchers, may help better understand pathological mechanisms that lead to the occurrence of this disease”.
Therefore, not only environment, hormonal stress in pregnancy and lifestyle as leading ADHD causes: date here indicate that all these factors could put roots particularly when the aforementioned gene variants are present.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Corominas J et al. , Lesch KP. Mol Psychiatry. 2018 Aug 16.
Hang X et al. PLoS One. 2017 Oct 27; 12(10):e0186570.
Langini C et al. J Biol Chem. 2017 Oct 6; 292(40):16734-745.
Dott. Gianfrancesco Cormaci
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