Functional effects of the DAT1 polymorphism on EEG measures in ADHD.

OBJECTIVE This paper examines whether dopamine transporter gene (DAT1) allele status mediates medication-related change in cognitive and neurophysiological measures among children with attention-deficiency/hyperactivity disorder (ADHD). METHOD A single 10-mg dose of methylphenidate was given in a double-blind, placebo-controlled fashion to children with ADHD who were seen for cognitive testing and EEG recording. Buccal samples were obtained and genotyped for the DAT1 polymorphism. RESULTS DAT1 allele status was associated with performance on a sustained attention task and medication-related EEG changes. Compared with those with one or more copies of the DAT1 9-repeat allele (9R), children with two copies of the 10-repeat allele (10R) exhibited poorer performance on the vigilance task. In addition, children with 10R exhibited medication-related EEG changes of increased central and parietal beta power, decreased right frontal theta power, and lower theta/beta ratios; 9R carriers showed the opposite pattern. CONCLUSIONS The data suggest that the DAT1 polymorphism mediates medication-related changes in cortical activity among children with ADHD.

[1]  B. Hjorth.  An on-line transformation of EEG scalp potentials into orthogonal source derivations. , 1975, Electroencephalography and clinical neurophysiology.

[2]  A. Schell,et al.  A cross-sectional and longitudinal study of age effects of electrophysiological measures in hyperactive and normal children. , 1984, Biological psychiatry.

[3]  J. Biederman,et al.  A family study of patients with attention deficit disorder and normal controls. , 1986, Journal of psychiatric research.

[4]  X Li,et al.  Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. , 1992, Genomics.

[5]  B. Pennington,et al.  Attention deficit disorder in reading-disabled twins: Evidence for a genetic etiology , 1992, Journal of abnormal child psychology.

[6]  C A Mann,et al.  Quantitative analysis of EEG in boys with attention-deficit-hyperactivity disorder: controlled study with clinical implications. , 1992, Pediatric neurology.

[7]  S. Amara,et al.  Neurotransmitter transporters: recent progress. , 1993, Annual review of neuroscience.

[8]  H. Engeland,et al.  Methylphenidate influences on both early and late ERP waves of ADHD children in a continuous performance test , 1994, Journal of abnormal child psychology.

[9]  N J Cox,et al.  Association of attention-deficit disorder and the dopamine transporter gene. , 1995, American journal of human genetics.

[10]  T Janzen,et al.  Differences in baseline EEG measures for ADD and Normally Achieving preadolescent males , 1995, Biofeedback and self-regulation.

[11]  K. Kidd,et al.  The dopamine transporter protein gene (SLC6A3): primary linkage mapping and linkage studies in Tourette syndrome. , 1995, Genomics.

[12]  R. Chabot,et al.  Sensitivity and Specificity of QEEG in Children with Attention Deficit or Specific Developmental Learning Disorders , 1996, Clinical EEG.

[13]  D I Boomsma,et al.  Heritability of human brain functioning as assessed by electroencephalography. , 1996, American journal of human genetics.

[14]  R. Chabot,et al.  Quantitative electroencephalographic profiles of children with attention deficit disorder , 1996, Biological Psychiatry.

[15]  S. Kuperman,et al.  Quantitative EEG differences in a nonclinical sample of children with ADHD and undifferentiated ADD. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[16]  R. Mark Wightman,et al.  Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter , 1996, Nature.

[17]  M. Gill,et al.  Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism , 1997, Molecular Psychiatry.

[18]  D. Javitt,et al.  Electrophysiological indices of information processing in methylphenidate responders , 1997, Biological Psychiatry.

[19]  H. Engeland,et al.  Effects of methylphenidate on event-related potentials and performance of attention-deficit hyperactivity disorder children in auditory and visual selective attention tasks , 1997, Biological Psychiatry.

[20]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[21]  Robert J Barry,et al.  EEG analysis in Attention-Deficit/Hyperactivity Disorder: a comparative study of two subtypes , 1998, Psychiatry Research.

[22]  C M Gómez,et al.  Frequency analysis of the EEG during spatial selective attention. , 1998, The International journal of neuroscience.

[23]  E Gordon,et al.  Quantified EEG Activity in Adolescent Attention Deficit Hyperactivity Disorder , 1998, Clinical EEG.

[24]  D I Boomsma,et al.  Genetic Influences on EEG Coherence in 5-Year-Old Twins , 1998, Behavior genetics.

[25]  I. Waldman,et al.  Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: heterogeneity owing to diagnostic subtype and severity. , 1998, American journal of human genetics.

[26]  H H Stassen,et al.  Familial brain wave patterns: study of a 12‐sib family , 1998, Psychiatric genetics.

[27]  J. Lubar,et al.  Methylphenidate effects on EEG, behavior, and performance in boys with ADHD. , 1998, Pediatric neurology.

[28]  Sandra K Loo,et al.  EEG correlates of methylphenidate response among children with ADHD: a preliminary report , 1999, Biological Psychiatry.

[29]  S. Nelson,et al.  No evidence of linkage or linkage disequilibrium between DAT1 and attention deficit hyperactivity disorder in a large sample. , 1999, Psychiatric genetics.

[30]  M. Gill,et al.  Mapping susceptibility loci in attention deficit hyperactivity disorder: preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children , 1999, Molecular Psychiatry.

[31]  J. Lubar,et al.  Methylphenidate effects on global and complex measures of EEG. , 1999, Pediatric neurology.

[32]  Darin D Dougherty,et al.  Dopamine transporter density in patients with attention deficit hyperactivity disorder , 1999, The Lancet.

[33]  Vincent J Monastra,et al.  Assessing attention deficit hyperactivity disorder via quantitative electroencephalography: an initial validation study. , 1999, Neuropsychology.

[34]  D. Comings,et al.  Association of the dopamine transporter gene (DAT1) with poor methylphenidate response. , 1999, Journal of the American Academy of Child and Adolescent Psychiatry.

[35]  J. Seibyl,et al.  Prediction of dopamine transporter binding availability by genotype: a preliminary report. , 2000, The American journal of psychiatry.

[36]  M I Posner,et al.  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. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Michael Murias,et al.  Dopamine genes and ADHD , 2000, Neuroscience & Biobehavioral Reviews.

[38]  Douglas W. Jones,et al.  Genotype Influences In Vivo Dopamine Transporter Availability in Human Striatum , 2000, Neuropsychopharmacology.

[39]  M. Owen,et al.  A family-based and case-control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder , 2000, Molecular Psychiatry.

[40]  A. Heath,et al.  Lack of association of dopamine D4 receptor gene polymorphisms with ADHD subtypes in a population sample of twins. , 2001, American journal of medical genetics.

[41]  L. Rohde,et al.  Attention-deficit hyperactivity disorder: a study of association with both the dopamine transporter gene and the dopamine D4 receptor gene. , 2001, American journal of medical genetics.

[42]  Robert J Barry,et al.  Age and sex effects in the EEG: differences in two subtypes of attention-deficit/hyperactivity disorder , 2001, Clinical Neurophysiology.

[43]  M. Nöthen,et al.  Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder , 2001, Biological Psychiatry.

[44]  R. Hen,et al.  Hyperactivity and impaired response habituation in hyperdopaminergic mice. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[45]  J. Lubar,et al.  The development of a quantitative electroencephalographic scanning process for attention deficit-hyperactivity disorder: reliability and validity studies. , 2001, Neuropsychology.

[46]  Carlos M. Gómez,et al.  Temporal evolution of α and β bands during visual spatial attention , 2001 .

[47]  R. Barry,et al.  EEG differences between good and poor responders to methylphenidate and dexamphetamine in children with attention-deficit/hyperactivity disorder , 2002, Clinical Neurophysiology.

[48]  H. Persson,et al.  Altered cortical activity in children with attention-deficit/hyperactivity disorder during attentional load task. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.