title: Possible effect of norepinephrine transporter polymorphisms on methylphenidate-induced changes in neuropsychological function in attention-deficit hyperactivity disorder.
abstract: BACKGROUND
  Dysregulation of noradrenergic system may play important roles in pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We examined the relationship between polymorphisms in the norepinephrine transporter SLC6A2 gene and attentional performance before and after medication in children with ADHD.
  
  
  METHODS
  Fifty-three medication-naïve children with ADHD were genotyped and evaluated using the continuous performance test (CPT). After 8-weeks of methylphenidate treatment, these children were evaluated by CPT again. We compared the baseline CPT measures and the post-treatment changes in the CPT measures based on the G1287A and the A-3081T polymorphisms of SLC6A2.
  
  
  RESULTS
  There was no significant difference in the baseline CPT measures associated with the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects with the G/G genotype at the G1287A polymorphism showed a greater decrease in the mean omission error scores (p = 0.006) than subjects with the G/A or A/A genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or A/T) showed a greater decrease in the mean commission error scores (p = 0.003) than those with the A/A genotypes.
  
  
  CONCLUSIONS
  Our results provide evidence for the possible role of the G1287A and A-3081T genotypes of SLC6A2 in methylphenidate-induced improvement in attentional performance and support the noradrenergic hypothesis for the pathophysiology of ADHD.
authors.affiliation: Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Subin
authors.initials: S
authors.lastname: Park
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Young-Hui
authors.initials: YH
authors.lastname: Yang
authors.forename: Soon-Beom
authors.initials: SB
authors.lastname: Hong
authors.forename: Min-Hyeon
authors.initials: MH
authors.lastname: Park
authors.forename: Boong-Nyun
authors.initials: BN
authors.lastname: Kim
authors.forename: Min-Sup
authors.initials: MS
authors.lastname: Shin
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Yoo
authors.forename: Soo-Churl
authors.initials: SC
authors.lastname: Cho
mesh_terms: D000293:Adolescent; D000483:Alleles; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D008774:Methylphenidate