[Genetic findings in Attention-Deficit and Hyperactivity Disorder (ADHD)].
Attention-Deficit and Hyperactivity Disorder (ADHD) is a common child and adolescent psychiatric disorder with a prevalence rate of 3-7%. Formal genetic studies provided an estimated heritability of 0.6-0.8 and an approximately five-fold elevated risk for ADHD in first-degree relatives. Currently, four genome scans have led to the identification of chromosomal regions potentially relevant in ADHD; especially the evidence for linkage to chromosome 5p13 is convincing. Meta-analyses of a large number of candidate gene studies suggest association with gene variants of the dopaminergic receptors DRD4 and DRD5, the serotonergic receptor HTR1B, and the synaptosomal receptor protein (SNAP-25). Hyperactivity has been investigated particularly in animal models, focusing on knockout- and quantitative trait loci (QTL) designs, with promising results for the dopaminergic system. It is likely that several gene polymorphisms with moderate to small effect sizes contribute to the phenotype ADHD; different combinations of such predisposing variants presumably underlie ADHD in different individuals. Therefore, large samples for molecular genetic studies are mandatory to detect these polymorphisms. Accordingly, several of today's findings have to be regarded as preliminary. The understanding of ADHD's neurobiology may be advanced by new technologies, such as SNP-based genome scans performed with gene chips comprising 10,000-1,000,000 SNPs, as well as using more sophisticated animal model designs.
Schimmelmann
Benno Graf
BG
Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters, Universität Duisburg-Essen, Rheinische Kliniken Essen, Virchowstrasse 174, DE-45147 Essen. bschimme@aol.com
Friedel
Susann
S
Christiansen
Hanna
H
Dempfle
Astrid
A
Hinney
Anke
A
Hebebrand
Johannes
J
D000293:Adolescent; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000235:genetics; D002648:Child; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D019955:Conduct Disorder / Q000235:genetics; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics; D012307:Risk Factors; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics
D044302:Receptor, Serotonin, 5-HT1B; D011954:Receptors, Dopamine; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25