Though there is little doubt that the serotonin system is a central player in the neurobiological response to nicotine, the precise role of the serotonin transporter or its associated alleles in smokers has yet to be elucidated. Researchers suggest that even pivotal regulatory proteins such as the serotonin transporter will only exhibit a moderate impact on complex behavioral phenotypes and may be obstructed by non-genetic influences, such as environmental factors (Lesch & Mossner, 1998). Indeed, some of the more robust relationships between the 5-HTTLPR gene and depression have been reported only in the presence of high levels of environmental stress (Caspi et al., 2003; Kendler, Kuhn, Vittum, Prescott, & Riley, 2005), though a recently published meta-analysis was unable to validate this relationship when combining the results of 14 studies comprised of over 14,000 participants (Risch et al., 2009). The authors reported that the relationship between stressful life events and depression was highly robust, but was not moderated by 5-HTTLPR genotype. However, the role of nicotine in these studies is unknown. The effect of genotype on smoking behavior and/or withdrawal is
