Spatial attentional bias as a marker of genetic risk, symptom severity, and stimulant response in ADHD

Neuropsychopharmacology. 2008 Sep;33(10):2536-45. doi: 10.1038/sj.npp.1301637. Epub 2007 Nov 28.

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a heritable childhood onset disorder that is marked by variability at multiple levels including clinical presentation, cognitive profile, and response to stimulant medications. It has been suggested that this variability may reflect etiological differences, particularly, at the level of underlying genetics. This study examined whether an attentional phenotype-spatial attentional bias could serve as a marker of symptom severity, genetic risk, and stimulant response in ADHD. A total of 96 children and adolescents with ADHD were assessed on the Landmark Task, which is a sensitive measure of spatial attentional bias. All children were genotyped for polymorphisms (3' untranslated (UTR) and intron 8 variable number of tandem repeats (VNTRs)) of the dopamine transporter gene (DAT1). Spatial attentional bias correlated with ADHD symptom levels and varied according to DAT1 genotype. Children who were homozygous for the 10-repeat allele of the DAT1 3'-UTR VNTR displayed a rightward attentional bias and had higher symptom levels compared to those with the low-risk genotype. A total of 26 of these children who were medication naive performed the Landmark Task at baseline and then again after 6 weeks of stimulant medication. Left-sided inattention (rightward bias) at baseline was associated with an enhanced response to stimulants at 6 weeks. Moreover, changes in spatial bias with stimulant medications, varied as a function of DAT1 genotype. This study suggests an attentional phenotype that relates to symptom severity and genetic risk for ADHD, and may have utility in predicting stimulant response in ADHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adolescent
  • Attention / drug effects
  • Attention / physiology*
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Central Nervous System Stimulants / pharmacology*
  • Central Nervous System Stimulants / therapeutic use
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Female
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Homozygote
  • Humans
  • Male
  • Minisatellite Repeats / genetics
  • Observer Variation
  • Perceptual Disorders / diagnosis
  • Perceptual Disorders / genetics
  • Perceptual Disorders / physiopathology
  • Polymorphism, Genetic / genetics
  • Risk Factors
  • Space Perception / drug effects
  • Space Perception / physiology*

Substances

  • 3' Untranslated Regions
  • Central Nervous System Stimulants
  • Dopamine Plasma Membrane Transport Proteins
  • Genetic Markers
  • Dopamine