Dopamine beta-hydroxylase gene (DbetaH) -1021C-->T influences self-reported paranoia during cocaine self-administration

Biol Psychiatry. 2007 Jun 1;61(11):1310-3. doi: 10.1016/j.biopsych.2006.08.012. Epub 2006 Dec 6.

Abstract

Background: Variation in the gene for dopamine beta-hydroxylase (DbetaH) has been reported to associate with cocaine-induced paranoia as assessed by retrospective self-report. This association has yet to be tested prospectively.

Methods: Visual analog scale (VAS) ratings of paranoia were obtained in 31 cocaine users during three cocaine self-administration sessions (8, 16, and 32 mg/70 kg). Pharmacogenetic interactions between cocaine and a putative functional polymorphism in DbetaH (-1021C-->T) were assessed.

Results: VAS self-ratings showed significant or trend-level interactions of genotype and time during each session (p = .004, .09 and .003, respectively) with TT homozygotes endorsing greater paranoia over time than either CT or CC individuals. Interactions were significant at all doses in African Americans (n = 19; p = .02, .04 and .05). No other demographic or experimental variable distinguished genotypic groups.

Conclusions: Results indicate that individuals homozygous for the 'very low-activity' T allele at DbetaH -1021C-->T show an increased propensity to paranoia over time during cocaine self-administration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Cocaine / administration & dosage
  • Cocaine-Related Disorders / genetics*
  • Cocaine-Related Disorders / psychology*
  • Dopamine beta-Hydroxylase / genetics*
  • Female
  • Genotype
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Paranoid Disorders / chemically induced
  • Paranoid Disorders / genetics*
  • Paranoid Disorders / psychology*
  • Polymorphism, Genetic / genetics
  • Prospective Studies
  • Reinforcement Schedule

Substances

  • Dopamine beta-Hydroxylase
  • Cocaine