Brain perfusion and dopaminergic genes in boys with attention-deficit/hyperactivity disorder

Am J Med Genet B Neuropsychiatr Genet. 2005 Jan 5;132B(1):53-8. doi: 10.1002/ajmg.b.30096.

Abstract

Neuroimaging studies have suggested the involvement of several brain areas in attention-deficit/hyperactivity disorder (ADHD). Genetic investigations have supported the role of both dopamine D4 receptor gene (DRD4) and dopamine transporter gene (DAT1) in the vulnerability to the disorder. This study evaluates whether the presence of risk alleles at DRD4 and/or DAT1 genes is associated with differences in regional cerebral blood flow (rCBF) in a sample of ADHD boys. The rCBF was compared between ADHD patients with and without risk alleles at DRD4 (7-repeat allele) and/or at DAT1 (homozygosis for the 10-repeat allele) genes by single photon emission computed tomography (SPECT) during continuous performance test. Images were analyzed using statistical parametric mapping (SPM-99). No significant differences in rCBF were found both between ADHD boys with and without the 7-repeat allele at DRD4 locus, as well as between ADHD boys homozygous for the 10-repeat allele and ADHD subjects with other genotypes at the DAT1 locus. However, a significantly higher perfusion in the right middle temporal gyrus was found in the group with risk alleles at both DRD4 and DAT1 loci (n = 6) compared to ADHD boys without risk alleles at both loci (n = 28) (P < 0.05). Our findings suggest that a higher recruitment in middle temporal gyrus, an area associated to working memory and selective attention, should exist to compensate a putative effect of the interaction between these dopaminergic genes.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Alleles
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Brain / blood supply*
  • Brain / diagnostic imaging
  • Cerebrovascular Circulation
  • Child
  • Dopamine Plasma Membrane Transport Proteins
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins / genetics*
  • Minisatellite Repeats / genetics
  • Nerve Tissue Proteins / genetics*
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D4
  • Tomography, Emission-Computed, Single-Photon

Substances

  • DRD4 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, Dopamine D2
  • SLC6A3 protein, human
  • Receptors, Dopamine D4