Background
Variation in the gene for dopamine β-hydroxylase (DβH) 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/70kg). Pharmacogenetic
interactions between cocaine and a putative functional polymorphism in DβH (-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 DβH -1021C→T show an increased propensity to paranoia over time during cocaine self-administration.
Key Words
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References
- Cocaine in the context of prior central nervous system stimulant epidemics.in: Volkow N.D. Swan A.C. Cocaine in the brain. Rutgers University Press, New Brunswick, NJ1990
- Selective sensitization to the psychosis-inducing effects of cocaine: A possible marker for addiction relapse vulnerability?.Neuropsychopharmacology. 1997; 16: 77-82
- Cocaine-induced psychosis.J Clin Psychiatry. 1991; 52: 509-512
- Nonparametric analysis of longitudinal data in factorial experiments. Wiley, New York2002
- Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: A randomized placebo-controlled trial.Arch Gen Psychiatry. 2004; 61: 264-272
- Rating the severity and character of transient cocaine-induced delusions and hallucinations with a new instrument, the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP).Drug Alcohol Depend. 2005; 80: 23-33
- A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia.Mol Psychiatry. 2000; 5: 56-63
- Genetic association between dopamine transporter protein alleles and cocaine-induced paranoia.Neuropsychopharmacology. 1994; 11: 195-200
- Genomewide linkage scan for cocaine dependence and related traits: Significant linkages for a cocaine-related trait and cocaine-induced paranoia.Am J Med Genet B Neuropsychiatr Genet. 2005; 136: 45-52
- A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson’s disease.Ann Neurol. 2004; 55: 443-446
- Risk factors for cocaine-induced paranoia in cocaine-dependent sibling pairs.Drug Alcohol Depend. 2006; 84: 77-84
- Self-reported paranoia during laboratory “binge” cocaine self-administration in humans.Pharmacol Biochem Behav. 2006; 83: 249-256
- A paradigm to investigate the regulation of cocaine self-administration in human cocaine users: A randomized trial.Psychopharmacology (Berl). 2006; 185: 306-314
- Preliminary observations of paranoia in a human laboratory study of cocaine.Addict Behav. 2006; 31: 1245-1251
- Intravenous cocaine infusions in humans: Dose responsivity and correlations of cardiovascular vs. subjective effects.Pharmacol Biochem Behav. 1989; 34: 697-703
- Cocaine-induced delirium versus delusional disorder.Biol Psychiatry. 1989; 26: 847-848
- Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts.Addiction. 2000; 95: 219-228
- Phenomenologic comparison of the idiopathic psychosis of schizophrenia and drug-induced cocaine and phencyclidine psychoses: A retrospective study.Clin Neuropharmacol. 1994; 17: 359-369
- Clinical features of cocaine-induced paranoia.Am J Psychiatry. 1991; 148: 495-498
Schank JR, Ventura R, Puglisi-Allegra S, Alcaro A, Cole CD, Liles LC, et al (in press): Dopamine beta-hydroxylase knockout mice have alterations in dopamine signaling and are hypersensitive to cocaine. Neuropsychopharmacology [Epub ahead of print].
- Suspiciousness induced by four-hour intravenous infusions of cocaine.Arch Gen Psychiatry. 1988; 45: 673-677
- A paradigm to investigate the self-regulation of cocaine administration in humans.Psychopharmacology (Berl). 2005; 180: 436-446
- A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: Evidence for a major functional polymorphism at the DBH locus.Am J Hum Genet. 2001; 68: 515-522
- The structure of linkage disequilibrium at the DBH locus strongly influences the magnitude of association between diallelic markers and plasma dopamine beta-hydroxylase activity.Am J Hum Genet. 2003; 72: 1389-1400
Article info
Publication history
Published online: December 08, 2006
Accepted:
August 17,
2006
Received in revised form:
August 16,
2006
Received:
June 12,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.