Attention-deficit/hyperactivity disorder and disruptive behavior disorders in adolescence related to levels of platelet MAO-B and polymorphisms in two candidate genes

摘要

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) and Disruptive BehaviorDisorders (DBD) (including Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD)),are common developmental and behaviour diagnoses among adolescents. Several of theirsymptoms, have been linked to genotypes (e.g. monoamine oxidase A Variable Number ofTandem Repeats (MAO-A VNTR) and the 5–HydroxyTryptamine Transporter gene-LinkedPolymorphic Region (5-HTT LPR)) as well as to platelet Monoamine oxidase B (MAO-B)activity.Aim: 1) To study the symptoms of ADHD and DBD phenotypes in adolescents and theirassociation with MAO-B activity in platelets, MAO-A VNTR and 5-HTT LPR genotypesseparately and in combination. 2) To describe the complexity of the phenotypes in relation tovarious psychiatric problems and risk behaviours. 3) To investigate psychiatric and behaviouralsymptoms separately, rather than the complete diagnosis and their association with individualand combinations of candidate genes.Methods:A population-based sample of twins including 177 girls and 135 boys was interviewedusing the Swedish version of Kiddie Schedule for Affective Disorders and Schizophrenia forSchool-Age Children-Present and Lifetime Version (K-SADS-PL). Diagnoses of ADHD andDBD were compiled based on the Diagnostic and Statistical Manual of Mental Disorders TextRevision (DSM-IV-TR) diagnostic criteria. Blood was drawn from the subjects and analysed forplatelet MAO-B activity and polymorphisms in the MAO-A VNTR and 5-HTT LPR genotypes.Results:1) For both boys and girls the heterozygote 5-HTT LPR genotype was found to berelated to symptoms of CD. Girls exhibited an association between low platelet MAO-B activityand symptoms of ODD and DBD. An association was found in boys between the short MAO-AVNTR allele and symptoms of DBD, as well as between ADHD-like problems and the presenceof a short 5-HTT LPR or short MAO-A VNTR allele, in combination with high levels of plateletMAO-B enzyme activity. 2) In girls, subthreshold diagnoses of ADHD and DBD coexisted withsymptoms of depression, mania, panic attacks, phobias, anorexia nervosa, motor tics and posttraumaticstress disorder (PTSD) while in boys with symptoms of depression and PTSD. In bothboys and girls, smoking and high alcohol consumption contributed to a high risk of having thesephenotypes. 3) The combination of low MAO-B activity in platelets and polymorphism in the 5-HTT LPR genotype was associated with several psychiatric symptoms.Conclusions:Polymorphisms in the 5-HTT LPR and MAO-A VNTR as well as MAO-Bactivity platelet separately and in combination are related to both ADHD and DBD. Thecomplexity of the ADHD and DBD phenotypes was shown by the association with severalpsychiatric and behavioural problems. A broad clinical assessment is needed for adolescents withsuch preliminary diagnoses and the serotonergic system should be further investigated whenstudying genetic influences on the complex ADHD and DBD phenotypes.