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.


CONCLUSIONS
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.
Malmberg
Kerstin
K
Karolinska 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. kerstin.malmberg@ki.se
Wargelius
Hanna-Linn
HL
Lichtenstein
Paul
P
Oreland
Lars
L
Larsson
Jan-Olov
JO
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000145:classification / Q000201:enzymology* / Q000523:psychology*; D001792:Blood Platelets / Q000201:enzymology; D004200:Diseases in Twins / Q000201:enzymology / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats; D008995:Monoamine Oxidase / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012727:Sex Characteristics; D013548:Sweden
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008995:Monoamine Oxidase