Interacting effects of the serotonin transporter gene and neuroticism in smoking practices and nicotine dependence

Individual differences in propensity to nicotine dependence appear to be me diated, in part, by genetic factors.' The serotonin transporter gene has a functional polymorphism (5-HTTLPR) which modulates gene transcription and r euptake.(2,3) A possible role in nicotine dependence is suggested by a link between 5-HTTLPR and neuroticism,(4) a personality trait which has been re lated to smoking practices.(5) In a cross-sectional study of 185 smokers, w e utilized multiple linear regression modeling to examine the interacting e ffects of the 5-HTTLPR and neuroticism on smoking practices and nicotine de pendence. Genotype was classified according to the presence or absence of t he short (s) allele vs the long (I) allele of 5-HTTLPR tie, s/s or s/l vs I /I). Models controlled for gender, age, race, and alcohol use. The 5-HTTLPR by neuroticism interaction effect was statistically significant in the mod els of nicotine intake (P = 0.05), nicotine dependence (P = 0.001), and smo king motivations (smoking to reduce negative mood (P = 0.01); smoking for s timulation (P = 0.01)), The results suggested that neuroticism was positive ly associated with these smoking practices among smokers with 5-HTTLPR S ge notypes (s/s or s/l), but not among smokers with the L genotype (I/I), The 5-HTTLPR may modify the effects of neuroticism on smoking motivations and n icotine dependence. Assessment of 5-HTTLPR genotype and neuroticism may hel p to identify smokers who are more responsive to psychotropic medications, such as selective serotonin reuptake inhibitors (SSRIs), which are being us ed in smoking cessation treatment.