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

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics - Tập 141B Số 5 - Trang 487-498 - 2006
Russell A. Barkley1, Karen Smith2, Mariellen Fischer3, Bradford Navia4
1Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York, USA
2Child Study Center, Yale University, New Haven, Connecticut
3Neuropsychology Service, Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
4Department of Neurology, Laboratories in Psychiatry, Tufts University Medical Center, New England Medical Center, Boston, Massachusetts

Tóm tắt

AbstractSeveral 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. © 2006 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

Achenbach T, 2001, Young Adult Behavior Checklist and Young Adult Self‐Report Forms

Achenbach TM, 1983, Manual for the Child Behavior Checklist and Revised Child Behavior Profile

Achenbach TM, 1986, Manual for the Teacher Report Form and the Child Behavior Profile

Achenbach TM, 1987, Manual for the Child Behavior Checklist–Youth Self‐Report Form

American Psychiatric Association, 1968, Diagnostic and statistical manual of mental disorders

American Psychiatric Association, 1987, Diagnostic and statistical manual of mental disorders

American Psychiatric Association, 2001, Diagnostic and statistical manual of mental disorders

Barkley RA, 1981, Hyperactive children: A handbook for diagnosis and treatment

Barkley RA, 1990, Attention deficit hyperactivity disorder: A clinical workbook

10.1007/BF00909976

10.1038/scientificamerican0998-66

10.1097/00004583-199007000-00007

10.1111/j.1469-7610.1991.tb00304.x

Barkley RA, 2002, The persistence of attention deficit hyperactivity disorder into young adulthood as a function of reporting source and definition of disorder, J Abnorm Psychol, 111, 279, 10.1037/0021-843X.111.2.279

10.1002/1096-8628(20000612)96:3<262::AID-AJMG5>3.0.CO;2-8

10.1016/j.neuropsychologia.2005.03.011

10.1097/00004583-199007000-00004

10.1001/archpsyc.1992.01820090056010

10.1176/ajp.152.3.431

10.1038/nrn896

10.1038/sj.mp.4000430

10.1001/jama.1991.03470130073032

10.1002/(SICI)1096-8628(19960531)67:3<264::AID-AJMG4>3.0.CO;2-N

10.1002/(SICI)1096-8628(19990820)88:4<358::AID-AJMG13>3.0.CO;2-G

10.1034/j.1399-0004.2000.570304.x

Cook EH, 1995, Association of attention‐deficit disorder and the dopamine transporter gene, Am J Hum Genet, 56, 993

10.1038/sj.mp.4000510

Dawkins R, 1982, The extended phenotype

10.1007/s10802-005-1829-8

10.1002/1096-8628(20000612)96:3<258::AID-AJMG4>3.0.CO;2-8

Faraone SV, 1999, Dopamine D4 Gene 7‐repeat allele and attention deficit hyperactivity disorder, Am J Psychiatry, 156, 768, 10.1176/ajp.156.5.768

10.1176/appi.ajp.158.7.1052

10.1037/0022-006X.58.5.580

10.1207/s15326942dn2701_5

10.1038/sj.mp.4000290

10.1001/archpsyc.1985.01790330017002

10.1097/00004583-199605000-00013

Gordon M, 1987, The Gordon diagnostic system

10.1521/adhd.2005.13.4.1

10.1007/BF00919127

10.1037/h0059831

10.1076/clin.13.1.12.1983

10.1002/1096-8628(20000612)96:3<268::AID-AJMG6>3.0.CO;2-#

10.1080/00049530410001734829

10.1176/appi.ajp.157.10.1700

10.1037/h0022886

10.1002/1096-8628(20000612)96:3<278::AID-AJMG8>3.0.CO;2-R

LaHoste GL, 1996, Dopamine D4 polymorphism is associated with attention deficit hyperactivity disorder, Mol Psychiatry, 1, 121

10.1176/appi.ajp.161.1.133

10.1097/01.chi.0000135622.05219.bf

10.1097/00004583-199706000-00009

10.1097/01.CHI.0000046890.27264.88

10.1176/appi.ajp.162.5.906

10.1002/(SICI)1096-8628(19990205)88:1<71::AID-AJMG13>3.0.CO;2-D

Mannuzza S, 1986, Mental disorders in the Community, 243

10.1001/archpsyc.1993.01820190067007

10.1176/ajp.155.4.493

10.1002/1096-8628(20000612)96:3<273::AID-AJMG7>3.0.CO;2-Z

10.1037/0022-3514.48.5.1316

10.1037/0021-843X.96.2.145

10.1097/00004583-200011000-00017

10.1037/0021-843X.108.1.24

10.1111/j.1469-7610.2004.00247.x

10.1037/h0035993

10.1038/sj.mp.4000432

10.1038/sj.mp.4000567

10.2466/pms.1994.78.1.63

10.2466/pms.1986.62.2.407

Ruff RM, 1992, The Ruff 2 and 7 Selective Attention Test: A neuropsychological application, Percept Motor Skills, 75, 1311, 10.2466/pms.1992.75.3f.1311

10.3109/02699059309008164

10.1097/00004583-199901000-00017

10.1056/NEJM198812153192404

Sinke RJ, 2000, Association analysis of the DRD4 and DAT1 genes in a Dutch ADHD population, Am J Hum Genet, 67, 1993

10.1038/sj.mp.4000457

10.1002/ajmg.b.20005

10.1038/sj.mp.4000354

10.1073/pnas.080070897

10.1016/S0149-7634(99)00062-7

10.1038/sj.mp.4000744

10.1192/bjp.174.2.105

10.1097/00004583-200012000-00015

10.1086/302132

Weiss G, 1993, Hyperactive children grown up

Werry J, 1970, Symptoms of psychopathology, 397

10.1176/appi.ajp.159.6.1046

10.1097/00004583-199912000-00006

Thông tin
Thông tin xuất bản

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Tập 141B Số 5

487-498

Thông tin tác giả