¹Lombardi Cancer Center (LCC), Georgetown University Medical Center, Washington, DC 20007, USA

²Pharmacogenetics Section, Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA

³Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19012, USA

⁴Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA

Correspondence to: Dr C Lerman LCC, Georgetown University Medical Center, 2233 Wisconsin Ave NW, Suite 317, Washington DC 20007-4104, USA. E-mail: lermanc@gunet.georgetown.edu

Individual differences in propensity to nicotine dependence appear to be mediated, in part, by genetic factors.1 The serotonin transporter gene has a functional polymorphism (5-HTTLPR) which modulates gene transcription and reuptake.23 A possible role in nicotine dependence is suggested by a link between 5-HTTLPR and neuroticism,4 a personality trait which has been related to smoking practices.5 In a cross-sectional study of 185 smokers, we utilized multiple linear regression modeling to examine the interacting effects of the 5-HTTLPR and neuroticism on smoking practices and nicotine dependence. Genotype was classified according to the presence or absence of the short (s) allele vs the long (l) allele of 5-HTTLPR (ie, s/s or s/l vs l/l). Models controlled for gender, age, race, and alcohol use. The 5-HTTLPR by neuroticism interaction effect was statistically significant in the models of nicotine intake (P = 0.05), nicotine dependence (P = 0.001), and smoking motivations (smoking to reduce negative mood (P = 0.01); smoking for stimulation (P = 0.01)). The results suggested that neuroticism was positively associated with these smoking practices among smokers with 5-HTTLPR S genotypes (s/s or s/l), but not among smokers with the L genotype (l/l). The 5-HTTLPR may modify the effects of neuroticism on smoking motivations and nicotine dependence. Assessment of 5-HTTLPR genotype and neuroticism may help to identify smokers who are more responsive to psychotropic medications, such as selective serotonin reuptake inhibitors (SSRIs), which are being used in smoking cessation treatment. Molecular Psychiatry (2000) 5, 189-192.

smoking; genetics; serotonin