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

Kerstin Malmberg,Hanna-Linn Wargelius,Jan-Olov Larsson,Paul Lichtenstein,Lars Oreland

doi:10.1186/1471-244x-8-28

Abstract

BackgroundPharmacological 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).MethodsA 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.ResultsWe 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.ConclusionOur 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.

Highlights

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)
In a population-based series of adolescent boys and girls, we investigated platelet Monoamine Oxidase B (MAO-B) activity and the candidate genes: monoamine oxidase A (MAO-A) (VNTR) and 5-hydroxytryptamine transporter (5-HTT) (LPR)
Our hypothesis that low platelet monoamine oxidase (MAO)-B activity is associated with high dimensions of the ADHD and DBD phenotype was verified only for DBD-symptoms in girls

Summary

Introduction

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). (ODD), are common child and adolescent psychiatric diagnoses They are disabling and associated with high costs, both for society and in terms of individual suffering. Research regarding these disorders in children and adolescents from the general population is important in order to identify risk factors related to the etiology and prognosis [1]. In the same way DBD includes two dimensions; CD, characterized by a variety of persistent antisocial behaviors including acts of aggression, destruction of property, deceitfulness, theft and violation of commonly adhered to social problems, and ODD, characterized by a sustained pattern of chronic argumentativeness and anger associated with compromised social relations with parents and peers [5]

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