In conclusion, our study is novel in that it is the first to demonstrate a relationship between a genotypic marker of 5-HT reuptake efficiency, and neural mehcanisms associated with appetitve and defensive activation. Smokers with the l/l genotype experienced a decrease in defensive responding (as measured by the startle respone) when given nicotine compared to smokers without the l allele, suggesting that l/l allele smokers experienced enhanced activation of appetitive mechanisms, which may be related to nicotine’s reinforcing effects and mood modulating properties. These results suggest that l/l smokers could be more likely to smoke to offset a potential deficit in serotonin by activating appetitive structutres with the consumption of nicotine. The small sample size in the current study represents a major limitation. It is possible that a larger sample would have revealed additional interactions between the variables of interest that might further elucidate the interplay between genotype and neural processes in smokers. However, given that large genetic studies often employ crude phenotypes such as smoker versus non-smoker that are so distal from specific neural processes in smokers, we believe
