Associations among types of impulsivity, substance use problems and neurexin-3 polymorphisms.

Abstract

BACKGROUND:

Some of the genetic vulnerability for addiction may be mediated by impulsivity. This study investigated relationships among impulsivity, substance use problems and six neurexin-3 (NRXN3) polymorphisms. Neurexins (NRXNs) are presynaptic transmembrane proteins that play a role in the development and function of synapses.

METHODS:

Impulsivity was assessed with the Barratt Impulsiveness Scale Version 11 (BIS-11), the Boredom Proneness Scale (BPS) and the TIME paradigm; alcohol problems with the Michigan Alcoholism Screening Test (MAST); drug problems with the Drug Abuse Screening Test (DAST-20); and regular tobacco use with a single question. Participants (n=439 Caucasians, 64.7% female) donated buccal cells for genotyping. Six NRXN3 polymorphisms were genotyped: rs983795, rs11624704, rs917906, rs1004212, rs10146997 and rs8019381. A dual luciferase assay was conducted to determine whether allelic variation at rs917906 regulated gene expression.

RESULTS:

In general, impulsivity was significantly higher in those who regularly used tobacco and/or had alcohol or drug problems. In men, there were modest associations between rs11624704 and attentional impulsivity (p=0.005) and between rs1004212 and alcohol problems (p=0.009). In women, there were weak associations between rs10146997 and TIME estimation (p=0.03); and between rs1004212 and drug problems (p=0.03). The dual luciferase assay indicated that C and T alleles of rs917906 did not differentially regulate gene expression in vitro.

CONCLUSIONS:

Associations between impulsivity, substance use problems and polymorphisms in NRXN3 may be gender specific. Impulsivity is associated with substance use problems and may provide a useful intermediate phenotype for addiction.

• Authors: Scott F Stoltenberg, Melissa K Lehmann, Christa C Christ, Samantha L Hersrud, Gareth E Davies
• Journal: Drug and alcohol dependence (Drug Alcohol Depend) Vol. 119 Issue 3 Pg. e31-8 (Dec 15 2011) ISSN: 1879-0046 [Electronic] Ireland
• PMID: 21676558 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Nerve Tissue Proteins
• neurexin IIIalpha

Topics

• Adolescent
• Adult
• Female
• Genetic Association Studies
• Humans
• Impulsive Behavior (diagnosis, epidemiology, genetics)
• Male
• Nerve Tissue Proteins (genetics)
• Polymorphism, Single Nucleotide
• Substance-Related Disorders (diagnosis, epidemiology, genetics)
• Surveys and Questionnaires
• Young Adult