title: An examination of the behavioral and neuropsychological correlates of three ADHD candidate gene polymorphisms (DRD4 7+, DBH TaqI A2, and DAT1 40 bp VNTR) in hyperactive and normal children followed to adulthood.
abstract: Several candidate gene polymorphisms have been implicated in attention deficit hyperactivity disorder (ADHD), including DAT1 40bp VNTR, DRD4 7+, and DBH TaqI A2 alleles. We used the Milwaukee longitudinal study of hyperactive (n = 122) and normal (n = 67) children to compare participants with and without these respective polymorphisms on ADHD-related behavioral ratings at childhood, 8 years later in adolescence, and 13+ years later into young adulthood. Neuropsychological tests were given at the adolescent and young adulthood follow-up. No differences were found between the DRD4-7+ and 7- repeat polymorphism. The DBH TaqI A2 allele, when homozygous, was associated with being more hyperactive in childhood, having more pervasive behavior problems at adolescence, and earning less money on a card playing task in adulthood. At adolescence, poorer test scores were also found only in the hyperactive group with homozygous for this allele. The DAT1 40bp VNTR heterozygous 9/10 repeat, however, differed from the 10/10 repeat pair in many respects, having greater ADHD and externalizing symptoms at all three follow-ups, more cross-situational behavioral problems at both childhood and adolescence, poorer mother-teen relations at adolescence, and lower class rankings in high school. Participants with the 9/10 pair in the control group also had lower work performance, a lower grade point average in high school, greater teacher rated externalizing symptoms at adolescence, and greater omission errors on a continuous performance test in adulthood. The DAT1 40bp VNTR 9/10 polymorphism pairing appears to be reliably associated with greater symptoms of ADHD and externalizing behavior from childhood to adulthood, and with family, educational, and occupational impairments. We also present a contrary view on the appropriate endophenotypes for use in behavioral genetic research on ADHD.
authors.affiliation: Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York, USA.
authors.forename: Russell A
authors.initials: RA
authors.lastname: Barkley
authors.forename: Karen M
authors.initials: KM
authors.lastname: Smith
authors.forename: Mariellen
authors.initials: M
authors.lastname: Fischer
authors.forename: Bradford
authors.initials: B
authors.lastname: Navia
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D001519:Behavior / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D004299:Dopamine beta-Hydroxylase; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases