Dopamine beta-hydroxylase gene (DbetaH) -1021C-->T influences self-reported paranoia during cocaine self-administration.
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.
Kalayasiri
Rasmon
R
Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06519, USA.
Sughondhabirom
Atapol
A
Gueorguieva
Ralitza
R
Coric
Vladimir
V
Lynch
Wendy J
WJ
Lappalainen
Jaakko
J
Gelernter
Joel
J
Cubells
Joseph F
JF
Malison
Robert T
RT
D000328:Adult; D000483:Alleles; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000523:psychology*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010259:Paranoid Disorders / Q000139:chemically induced / Q000235:genetics* / Q000523:psychology*; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D012055:Reinforcement Schedule
D004299:Dopamine beta-Hydroxylase; D003042:Cocaine