Aggressiveness in Italian Children with ADHD: MAOA Gene Polymorphism Involvement

Abstract

ADHD is a neurodevelopmental disorder that children and adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls. We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p = 0.02 and p = 0.03, respectively), whereas the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p = 0.0002 and p = 0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highlighted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness, suggesting that these genotypes may be protective towards specific changes in behavior (p = 0.05). Interestingly, an increase in the GG genotype of rs6323 (p = 0.01) and a decrease in GT genotype (p = 0.0005) was also found in patients without aggressive behavior compared to controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help in the early detection of patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

Keywords: 5-HTT; ADHD; MAOA; aggressive behavior.

Figure 1

Multiple genetic variants are involved in ADHD development. As in most psychiatric diseases, genetic and environmental factors precociously affect the development of the central nervous system. The interaction between genetic predisposition and the environment, including adverse events that occur in the individual’s life (so-called stressors), may induce certain behaviors or psychological disorders. The relationship between genetic and environmental risk factors that may underlie interindividual variability and susceptibility to ADHD and/or impulsive aggressive behavior are shown here. The Figure was created with Biorender.