Neurexins (NRXNs) are presynaptic transmembrane proteins that primarily act as cell adhesion molecules, but are also known to play a role in neuronal synapse function and development [92]. They are hypothesized to mediate impulsivity and therefore may be implicated in genetic vulnerability for opioid dependence [92]. In a genome-wide study, Lachman et al. [93] found an association between opioid dependence and a wide region of chromosome 14q (exclusive to the Puerto Rican subpopulation) where the NRXN3 gene is located. Similarly, Stoltenberg et al [92] assessed six SNPs in the NRXN3 gene for associations between substance use problems, impulsivity, and these genetic polymorphisms. Using self-report questionnaires to assess impulsivity and health-risk behaviours [92], Stoltenberg et al reported that one SNP (rs11624704) was associated with impulsivity in men but not women, and that higher impulsivity is more common with regular tobacco and alcohol use [92]. Although the study did not find significant results with regards to opioid dependence, impulsivity may be indirectly linked to substance use disorders including opioid dependence and further research may elucidate a direct association between NRXN3 SNPs and opioid dependence.
