title: 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.affiliation: Department of Psychology, University of Nebraska-Lincoln, Lincoln, 221 Burnett Hall, PO Box 880308, NE 68588-0308, USA. sstoltenberg2@unl.edu
authors.forename: Scott F
authors.initials: SF
authors.lastname: Stoltenberg
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Lehmann
authors.forename: Christa C
authors.initials: CC
authors.lastname: Christ
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Hersrud
authors.forename: Gareth E
authors.initials: GE
authors.lastname: Davies
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007175:Impulsive Behavior / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins; C082354:neurexin IIIalpha