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

Kerstin Malmberg^*¹ , Hanna-Linn Wargelius^*² , Paul Lichtenstein³ , Lars Oreland² and Jan-Olov Larsson¹

¹Karolinska Institutet, Department of Woman and Child Health, Child and Adolescent Psychiatric Unit Q3:04, Astrid Lindgren Children's Hospital, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden

²Uppsala University, Department of Neuroscience, Sweden

³Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Sweden

author email corresponding author email* Contributed equally

BMC Psychiatry 2008, 8:28doi:10.1186/1471-244X-8-28


Published:	23 April 2008

Abstract

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.