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

ABSTRACT 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.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 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. Access through your institution Buy or

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supported by National Institutes of Health grant CA63562. The authors would like to thank Chris Borillo, Anna Ryan Robertson, Irene Angel, and Susan Marx for their assistance with data

collection and report preparation, and Brian Cobb for assistance with genotyping. We also appreciate the very helpful comments of Dr Dean Hamer. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Lombardi Cancer Center (LCC), Georgetown University Medical Center, Washington, 20007, DC, USA C Lerman, J Audrain & D Main * Pharmacogenetics Section, Genetic Epidemiology Branch,

National Cancer Institute, Bethesda, 20892, MD, USA N E Caporaso * Division of Population Science, Fox Chase Cancer Center, Philadelphia, 19012, PA, USA N R Boyd * Molecular Epidemiology

Section, Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, 20892, MD, USA P G Shields Authors * C Lerman View author publications You can also search for this author

inPubMed Google Scholar * N E Caporaso View author publications You can also search for this author inPubMed Google Scholar * J Audrain View author publications You can also search for this

author inPubMed Google Scholar * D Main View author publications You can also search for this author inPubMed Google Scholar * N R Boyd View author publications You can also search for this

author inPubMed Google Scholar * P G Shields View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to C Lerman. RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lerman, C., Caporaso, N., Audrain, J. _et al._ Interacting effects of the serotonin transporter gene and neuroticism

in smoking practices and nicotine dependence. _Mol Psychiatry_ 5, 189–192 (2000). https://doi.org/10.1038/sj.mp.4000672 Download citation * Received: 07 June 1999 * Revised: 25 August 1999

* Accepted: 25 August 1999 * Published: 15 May 2000 * Issue Date: 01 March 2000 * DOI: https://doi.org/10.1038/sj.mp.4000672 SHARE THIS ARTICLE Anyone you share the following link with will

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content-sharing initiative KEYWORDS * smoking * genetics * serotonin