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 = .005) and between rs1004212 and alcohol problems (p = .009). In women, there were weak associations between rs10146997 and TIME estimation (p = .03); and between rs1004212 and drug problems (p = .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.

The factors that influence individual differences in decision making are not yet fully characterized, but convergent evidence is accumulating that implicates serotonin (5-HT) system function. Therefore, both genes and environments that influence serotonin function are good candidates for association with risky decision making. In the present study we examined associations between common polymorphisms in the serotonin transporter gene (SLC6A4; 5-HTTLPR and rs25531), the experience of childhood trauma and decision making on the Iowa gambling task (IGT) in 391 (64.5% female) healthy Caucasian adults. Homozygosity for the 5-HTTLPR L allele was associated with riskier decision making in the first block of 20 trials (i.e., decision making under ambiguity, p = 0.004). In addition, mean IGT performance was significantly worse in blocks 3–5 (i.e., decision making under risk, p ≤ 0.05) for those participants who reported experiencing higher levels of childhood trauma. Our findings add to the growing evidence that genetic variation in the 5-HT system is associated with individual differences in decision making under ambiguity; and we report that the experience of childhood trauma is associated with relatively poor decision making under risk.