Association between dopamine transporter (DATI) genotype, left-sided inattention, and an enhanced response to methylphenidate in attention-deficit hyperactivity disorder

被引:77
作者
Bellgrove, MA
Hawi, Z
Kirley, A
Fitzgerald, M
Gill, M
Robertson, IH
机构
[1] Univ Dublin Trinity Coll, Dept Psychol, Dublin 2, Ireland
[2] Univ Dublin Trinity Coll, Inst Neurosci, Dublin 2, Ireland
[3] Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland
[4] Univ Dublin Trinity Coll, Dept Genet, Dublin 2, Ireland
关键词
DATI; dopamine; ADHD; methylphenidate; attention; genetics;
D O I
10.1038/sj.npp.1300839
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
A polymorphism of the dopamine transporter gene (DAT1, 10-repeat) is associated with attention-deficit hyperactivity disorder (ADHD) and has been linked to an enhanced response to methylphenidate (MPH). One aspect of the attention deficit in ADHD includes a subtle inattention to left space, resembling that seen after right cerebral hemisphere damage. Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether left-sided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH. A total of 43 ADHD children and their parents were genotyped for the DAT1 30 variable number of tandem repeats polymorphism. The children performed the Landmark Test, a well-validated measure yielding a spatial attentional asymmetry index ( leftward to rightward attentional bias). Parents rated their child's response to MPH retrospectively using a three-point scale ( no, mediocre or very good response). Additionally, parents used a symptom checklist to rate behavior while on and off medication. A within-family control design determined whether asymmetry indices predicted biased transmission of 10-repeat parental DAT1 alleles and/or response to MPH. It was found that left-sided inattention predicted transmission of the 10-repeat allele from parents to probands and was associated with the severity of ADHD symptomatology. Children rated as achieving a very good response to MPH displayed left-sided inattention, while those rated as achieving a poorer response did not. Our results suggest a subgroup of children with ADHD for whom the 10-repeat DAT1 allele is associated with left-sided inattention. MPH may be most efficacious in this group because it ameliorates a DAT1-mediated hypodopaminergic state.
引用
收藏
页码:2290 / 2297
页数:8
相关论文
共 52 条
[41]   Methylphenidate-evoked changes in striatal dopamine correlate with inattention and impulsivity in adolescents with attention deficit hyperactivity disorder [J].
Rosa-Neto, P ;
Lou, HC ;
Cumming, P ;
Pryds, O ;
Karrebaek, H ;
Lunding, J ;
Gjedde, A .
NEUROIMAGE, 2005, 25 (03) :868-876
[42]   Effects of stimulant medication on the lateralisation of line bisection judgements of children with attention deficit hyperactivity disorder [J].
Sheppard, DM ;
Bradshaw, JL ;
Mattingley, JB ;
Lee, P .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1999, 66 (01) :57-63
[43]   Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder [J].
Sowell, ER ;
Thompson, PM ;
Welcome, SE ;
Henkenius, AL ;
Toga, AW ;
Peterson, BS .
LANCET, 2003, 362 (9397) :1699-1707
[44]   Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention [J].
Swanson, J ;
Oosterlaan, J ;
Murias, M ;
Schuck, S ;
Flodman, P ;
Spence, MA ;
Wasdell, M ;
Ding, YC ;
Chi, HC ;
Smith, M ;
Mann, M ;
Carlson, C ;
Kennedy, JL ;
Sergeant, JA ;
Leung, P ;
Zhang, YP ;
Sadeh, A ;
Chen, CS ;
Whalen, CK ;
Babb, KA ;
Moyzis, R ;
Posner, MI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (09) :4754-4759
[45]   Functional deficits in basal ganglia of children with attention-deficit/hyperactivity disorder shown with functional magnetic resonance imaging relaxometry [J].
Teicher, MH ;
Anderson, CM ;
Polcari, A ;
Glod, CA ;
Maas, LC ;
Renshaw, PF .
NATURE MEDICINE, 2000, 6 (04) :470-473
[46]   Selective effects of methylphenidate in attention deficit hyperactivity disorder: A functional magnetic resonance study [J].
Vaidya, CJ ;
Austin, G ;
Kirkorian, G ;
Ridlehuber, HW ;
Desmond, JE ;
Glover, GH ;
Gabrieli, JDE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (24) :14494-14499
[47]  
VOELLER KKS, 1988, NEUROLOGY, V38, P806
[48]   Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate [J].
Volkow, ND ;
Wang, GJ ;
Fowler, JS ;
Gatley, SJ ;
Logan, J ;
Ding, YS ;
Hitzemann, R ;
Pappas, N .
AMERICAN JOURNAL OF PSYCHIATRY, 1998, 155 (10) :1325-1331
[49]   Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: Heterogeneity owing to diagnostic subtype and severity [J].
Waldman, ID ;
Rowe, DC ;
Abramowitz, A ;
Kozel, ST ;
Mohr, JH ;
Sherman, SL ;
Cleveland, HH ;
Sanders, ML ;
Card, JHC ;
Stever, C .
AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 63 (06) :1767-1776
[50]   A logistic regression based extension of the TDT for continuous and categorical traits [J].
Waldman, ID ;
Robinson, BF ;
Rowe, DC .
ANNALS OF HUMAN GENETICS, 1999, 63 :329-340