Contribuição de polimorfismos funcionais em genes do sistema monoaminérgico para a ansiedade matemática em crianças em idade escolar

Abstract

Math anxiety (MA) is a specific subtype of anxiety that affects mathematical skills. It manifests as symptoms of discomfort, tension, and fear of activities involving math and it can interfere with number manipulation and in solving arithmetic problems. Therefore, MA can affect the individual's performance both in the school environment and in everyday life. MA is a condition that manifests at the beginning of school life and it can persist until adulthood, causing, among other outcomes, poor performance, difficulty in managing financial resources and the avoidance of careers in STEM. MA is a multifactorial phenotype, therefore environmental factors such as poor teaching quality, math anxious teachers and adverse learning environment can contribute to the emergence and worsening of MA. These and other environmental factors have been extensively investigated over the last 50 years. However, it is known that genetic factors also contribute to a considerable portion of the phenotypic variance of MA. Nevertheless, to date, only one study has proposed to identify the genetic-molecular causes of this trait using a candidate gene association approach. Given the absence of genetic studies for MA, the neurobiological and quantitative evidence of the existence of genetic components and the success of the first study to propose as a candidate, a gene involved in neurotransmitter metabolism important for math cognition and emotion processing, the present study aimed at investigating other candidate genes for MA. Therefore, the aim of this study was to investigate the contribution of functional polymorphisms in three genes responsible for the modulation of the monoaminergic system (SLC6A4, MAOA and MAOB) to MA in a sample of school-age children. As a result, heterosis at the 5-HTTLPR locus in the SLC6A4 gene were found to be a risk factor for high levels of MA. In contrast, heterozygosity at the MAOA-LPR locus in the MAOA gene in girls was a protective factor for MA, and this effect was restricted to females. For the locus rs1799836 in the MAOB gene, the effect was more pronounced in boys and an interaction between sex and G/G genotype in girls and G genotype in boys was described herein. This is the second study to identify genes associated with MA. The results described herein reinforce the existence of genetic factors contributing to MA and reveal that the effects of allelic substitution in the investigated loci vary according to sex, and can be restricted to only one sex, or have opposite effects regarding sex. Furthermore, the results suggest that in association studies for monoaminergic system polymorphisms, different genotypic models should be tested for each sex.