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.

Full 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.(c) 2006 Wiley-Liss, Inc.

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Author information

Author/s: Barkley, Russell A (RA); Smith, Karen M (KM); Fischer, Mariellen (M); Navia, Bradford (B);

Affiliation: Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York, USA.

Grants: MH42181 (Agency:NIMH NIH HHS) ; R01 MH042181-12 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet), published in United States. (Language: eng)

Reference: 2006-Jul; vol 141B (issue 5) : pp 487-98

Dates: Created 2006/06/19; Completed 2006/08/16; Revised 2008/10/08;

PMID: 16741944, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adolescent
Adult
Alleles
Attention Deficit Disorder with Hyperactivity - genetics; physiopathology; psychology
Behavior - physiology
Child
Child, Preschool
Deoxyribonucleases, Type II Site-Specific - metabolism
Dopamine Plasma Membrane Transport Proteins - genetics
Dopamine beta-Hydroxylase - genetics; metabolism
Female

Female
Gene Frequency
Genetic Predisposition to Disease - genetics
Genotype
Humans
Longitudinal Studies
Male
Minisatellite Repeats - genetics
Neuropsychological Tests
Polymorphism, Genetic
Receptors, Dopamine D4 - genetics

Associated Chemicals: Dopamine Plasma Membrane Transport Proteins (0) ; SLC6A3 protein, human (0) ; Receptors, Dopamine D4 (137750-34-6) ; Dopamine beta-Hydroxylase (EC 1.14.17.1) ; Deoxyribonucleases, Type II Site-Specific (EC 3.1.21.4) ; TCGA-specific type II deoxyribonucleases (EC 3.1.21.4)

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