ADHD and Disruptive behavior scores - associations with MAO-A and 5-HTT genes and with platelet MAO-B activity in adolescents

Background: Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of Attention Deficit Hyperactivity Disorder ( ADHD) and Disruptive Behavior Disorder ( DBD). We have, in a population-based sample, studied associations between dimensions of the ADHD/DBD phenotype and Monoamine Oxidase B ( MAO-B) activity in platelets and polymorphisms in two serotonergic genes: the Monoamine Oxidase A Variable Number of Tandem Repeats ( MAO-A VNTR) and the 5-Hydroxytryptamine Transporter gene-Linked Polymorphic Region ( 5- HTT LPR). Methods: A population-based sample of twins, with an average age of 16 years, was assessed for ADHD/DBD with a clinical interview; Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). Blood was drawn from 247 subjects and analyzed for platelet MAO-B activity and polymorphisms in the MAO-A and 5- HTT genes. Results: We found an association in girls between low platelet MAO-B activity and symptoms of Oppositional Defiant Disorder ( ODD). In girls, there was also an association between the heterozygote long/short 5- HTT LPR genotype and symptoms of conduct disorder. Furthermore the heterozygote 5- HTT LPR genotype in boys was found to be associated with symptoms of Conduct Disorder ( CD). In boys, hemizygosity for the short MAO-A VNTR allele was associated with disruptive behavior. Conclusion: Our study suggests that the serotonin system, in addition to the dopamine system, should be further investigated when studying genetic influences on the development of Disruptive Behavior Disorders.