Interaction between the serotonin transporter gene and neuroticism in cigarette smoking behavior

Cigarette smoking behavior is influenced by both personality traits and inh erited factors. Previous research showed that neuroticism-a broad personali ty domain that includes anxiety, depression, impulsiveness and vulnerabilit y-increases the risk of being a smoker, primarily because of difficulty in quitting. Neuroticism has also been associated with the 5-HTTLPR, a functio nal polymorphism in the promoter for the serotonin transporter gene. We use d population and family-based methods to analyze the joint effects of the 5 -HTTLPR and neuroticism on smoking behavior in a population of 759 never, c urrent, and former smokers, all members of sib-pairs, Our main finding is t hat smoking behavior is influenced by an interaction between neuroticism an d 5-HTTLPR genotype. Specifically, neuroticism was positively correlated wi th current smoking and negatively associated with smoking cessation in indi viduals and siblings with poorly transcribed 5-HTTLPR-S genotypes, but not in those with the more highly expressed 5-HTTLPR-L genotype, Individuals wi th both a 5-HTTLPR-S genotype and a high level of neuroticism had the great est difficulty in quitting smoking. These data, if replicated, suggest that smoking behavior is more strongly influenced by the combination of the ser otonin transporter gene and neuroticism than by either factor alone, and th at personality scores and 5-HTTLPR genotype may predict the clinical effica cy of certain smoking cessation drugs.