The Genetic Basis for Vulnerability to Substance Abuse

Allelic Linkage in Substance Abuse

This investigation seeks to better define the genetic basis for vulnerability to substance abuse.

Study Overview

• Status: Completed
• Conditions: Substance Abuse
• Intervention / Treatment: Procedure: Blood draw

Detailed Description

Dopamine (DA), a neurotransmitter helping to mediate reward and reinforcement, has been putatively linked to the development of substance abuse, alcohol abuse, and alcoholism. Identification of specific vulnerability-association alleles for receptors, other molecules within the reward mediating system, and other genes that may predispose individuals to the development of such disorders is the goal of the study.

This investigation will help elucidate the genetic underpinnings of substance abuse, potentially leading to the improved methods to diagnose those at risk and to help develop better therapeutic interventions.

• Study Type: Observational
• Enrollment (Anticipated): 8000

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • National Institute on Drug Abuse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Substance abusers
• Allow for blood draw

Exclusion Criteria:

• Cognitively impaired

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: George Uhl, M.D., Ph.D., National Institute on Drug Abuse (NIDA)

Publications and helpful links

General Publications

• Grandy DK, Litt M, Allen L, Bunzow JR, Marchionni M, Makam H, Reed L, Magenis RE, Civelli O. The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a TaqI RFLP. Am J Hum Genet. 1989 Nov;45(5):778-85.
• Noble EP, Blum K, Khalsa ME, Ritchie T, Montgomery A, Wood RC, Fitch RJ, Ozkaragoz T, Sheridan PJ, Anglin MD, et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend. 1993 Oct;33(3):271-85. doi: 10.1016/0376-8716(93)90113-5. Erratum In: Drug Alcohol Depend 1993 Dec;34(1):83-4.
• Clark CJ, Downie CC. A method for the rapid determination of the number of patients to include in a controlled clinical trial. Lancet. 1966 Dec 17;2(7477):1357-8. doi: 10.1016/s0140-6736(66)92098-8. No abstract available.
• Hill SY, Armstrong J, Steinhauer SR, Baughman T, Zubin J. Static ataxia as a psychobiological marker for alcoholism. Alcohol Clin Exp Res. 1987 Aug;11(4):345-8. doi: 10.1111/j.1530-0277.1987.tb01323.x.
• Shigeta Y, Ishii H, Takagi S, Yoshitake Y, Hirano T, Takata H, Kohno H, Tsuchiya M. HLA antigens as immunogenetic markers of alcoholism and alcoholic liver disease. Pharmacol Biochem Behav. 1980;13 Suppl 1:89-94. doi: 10.1016/s0091-3057(80)80014-1.
• Smith SS, O'Hara BF, Persico AM, Gorelick DA, Newlin DB, Vlahov D, Solomon L, Pickens R, Uhl GR. Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers. Arch Gen Psychiatry. 1992 Sep;49(9):723-7. doi: 10.1001/archpsyc.1992.01820090051009.
• Uhl GR, Liu QR, Walther D, Hess J, Naiman D. Polysubstance abuse-vulnerability genes: genome scans for association, using 1,004 subjects and 1,494 single-nucleotide polymorphisms. Am J Hum Genet. 2001 Dec;69(6):1290-300. doi: 10.1086/324467. Epub 2001 Nov 6.
• Moolchan ET, Radzius A, Epstein DH, Uhl G, Gorelick DA, Cadet JL, Henningfield JE. The Fagerstrom Test for Nicotine Dependence and the Diagnostic Interview Schedule: do they diagnose the same smokers? Addict Behav. 2002 Jan-Feb;27(1):101-13. doi: 10.1016/s0306-4603(00)00171-4.
• Uhl GR, Liu QR, Naiman D. Substance abuse vulnerability loci: converging genome scanning data. Trends Genet. 2002 Aug;18(8):420-5. doi: 10.1016/s0168-9525(02)02719-1.
• Stein L, Belluzzi J. Second messengers, natural rewards, and drugs of abuse. Clin Neuropharmacol. 1986;9 Suppl 4:205-7. No abstract available.
• Uhl GR, Gold LH, Risch N. Genetic analyses of complex behavioral disorders. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):2785-6. doi: 10.1073/pnas.94.7.2785. No abstract available.
• Uhl GR, Persico AM, Smith SS. Current excitement with D2 dopamine receptor gene alleles in substance abuse. Arch Gen Psychiatry. 1992 Feb;49(2):157-60. doi: 10.1001/archpsyc.1992.01820020068010. No abstract available.
• Johnson EO, van den Bree MB, Uhl GR, Pickens RW. Indicators of genetic and environmental influences in drug abusing individuals. Drug Alcohol Depend. 1996 May;41(1):17-23. doi: 10.1016/0376-8716(96)01223-9.
• Uhl GR. Molecular genetics of substance abuse vulnerability: a current approach. Neuropsychopharmacology. 1999 Jan;20(1):3-9. doi: 10.1016/S0893-133X(98)00061-X. No abstract available.
• Wise RA. Action of drugs of abuse on brain reward systems. Pharmacol Biochem Behav. 1980;13 Suppl 1:213-23. doi: 10.1016/s0091-3057(80)80033-5. No abstract available.
• Gelernter J, Moises H, Grandy D, et al. Exclusion of schizophrenia triat from regions of the D2 dopamine receptor and prophobilinogen deaminase genes. In: 28th Annual Meeting, American College of Neurophyschopharmacology, December 13, 1980; Maui, Hawaii, Abstracts p.216.
• Wyatt RJ, Farouk K, Suddath R, Hitri A. The role of dopamine in cocaine use and abuse. Psychiatric Annals 1988; 18:531-534.

Study record dates

Study Major Dates

• Study Start: August 1, 1992
• Primary Completion (Actual): February 1, 2006
• Study Completion (Actual): February 1, 2006

Study Registration Dates

• First Submitted: October 31, 2005
• First Submitted That Met QC Criteria: October 31, 2005
• First Posted (Estimate): November 2, 2005

Study Record Updates

• Last Update Posted (Estimate): January 12, 2017
• Last Update Submitted That Met QC Criteria: January 11, 2017
• Last Verified: October 1, 2005

More Information

Terms related to this study

• Keywords: Substance abuse
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: NIDA-IRP-148