Rationale: Hyperactivity, impulsivity, and inattention are major symptoms occurring in attention-deficit/hyperactivity disorder. This disorder is highly heritable, multifactorial, polygenic, and associated primarily with dysfunctions of dopaminergic, noradrenergic, and serotonergic systems.
Objectives: The present study tested the possible association of the catechol-O-methyltransferase (COMT) Val108/158Met (rs4680) polymorphism with hyperactive-impulsive and inattentive symptoms in male youth.
Method: Polymorphism COMT Val108/158Met was analyzed in 807 male unrelated Caucasian young subjects: 231 healthy controls, 195 subjects with moderate hyperactive symptoms and 254 subjects with moderate inattentive symptoms, 111 subjects with severe hyperactive symptoms and 90 subjects with severe inattentive symptoms, all evaluated using Swanson, Nolan, and Pelham Questionnaire IV criteria.
Results: The frequency of the COMT genotypes, alleles, and the homozygous Met/Met genotype versus Val carriers (χ²) test with standardized residuals) differed significantly between subjects without and subjects with hyperactive-impulsive and inattentive symptoms. In addition, significantly higher hyperactive-impulsive and inattentive scores were found in subjects with the Met/Met genotype compared to carriers of other COMT genotypes. These significant results were due to the more frequent occurrence of Met/Met genotype or the Met allele in subjects with moderate and severe hyperactive-impulsive and inattentive symptoms compared to matched controls.
Conclusion: These results suggest that the Met/Met genotype or the Met allele of the COMT Val108/158Met, contributing to higher dopaminergic activity, are significantly overrepresented in subjects with moderate or severe hyperactive-impulsive and inattentive symptoms, and that this polymorphism is significantly associated with hyperactive-impulsive and inattentive symptoms in young boys and adolescents.