Cortical dopamine dysfunction in symptomatic and premanifest Huntington's disease gene carriers

Neurobiol Dis. 2010 Feb;37(2):356-61. doi: 10.1016/j.nbd.2009.10.015. Epub 2009 Oct 22.

Abstract

We used (11)C-raclopride PET, a marker of D(2) dopamine receptor binding, and statistical parametric mapping (SPM) to localise cortical D(2) receptor dysfunction in individual Huntington's disease (HD) gene carriers (16 symptomatic and 11 premanifest subjects) and assess its clinical significance. 62.5% of symptomatic HD patients and 54.5% of premanifest carriers showed cortical reductions in D(2) binding. The most frequent decreases in cortical binding in individual HD subjects were seen in temporal and frontal areas. Symptomatic HD subjects with decreased cortical D(2) binding had worse scores on neuropsychological tests assessing attention and executive functions than subjects without cortical dopamine dysfunction, notwithstanding comparable reduction in striatal D(2) binding and motor disability. Our results indicate that cortical dopaminergic dysfunction is common in both symptomatic and premanifest HD gene carriers. It is an early event in HD pathophysiology and could contribute to the impairment in neuropsychological performance in these patients.

MeSH terms

  • Adult
  • Binding, Competitive / genetics
  • Carbon Radioisotopes
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / physiopathology
  • Dopamine / metabolism*
  • Dopamine Antagonists / metabolism
  • Female
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / metabolism
  • Frontal Lobe / physiopathology
  • Genetic Markers / genetics
  • Heterozygote
  • Humans
  • Huntington Disease / genetics*
  • Huntington Disease / metabolism*
  • Huntington Disease / physiopathology
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Predictive Value of Tests
  • Prognosis
  • Raclopride / metabolism
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D2 / metabolism*
  • Temporal Lobe / diagnostic imaging
  • Temporal Lobe / metabolism
  • Temporal Lobe / physiopathology

Substances

  • Carbon Radioisotopes
  • Dopamine Antagonists
  • Genetic Markers
  • Receptors, Dopamine D2
  • Raclopride
  • Dopamine