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Bad combination: Neuroticism, a gene, and cigarettes
Edward R. Winstead

Quitting smoking is tougher for people with a certain personality and a certain gene, according to two new studies. Smokers with neurotic traits and a form of the serotonin transporter gene are less likely to kick the habit than are smokers who have only the trait or the gene, suggesting that smoking is influenced by the gene-trait combination.

Both the brain chemical serotonin and neuroticism are risk factors for smoking, and medications that affect serotonin have been used to help smokers get off cigarettes. These studies are the first to document an interaction between a genetic predisposition for smoking and a personality trait.

One gene and a 240-item questionnaire

The first study, led by Dean Hamer, of the National Cancer Institute, started with the hypothesis that smokers, former smokers, and non-smokers have different forms of the serotonin transporter gene. (The "long" and "short" variants of the gene are expressed differently, affecting serotonin levels in the brain.) This hypothesis proved to be wrong. No associations between the different forms of the gene and smoking habits were found in a sample of 759 people.

But the researchers did find support for their second, more speculative, hypothesis: that smoking is influenced by interactions between the gene variant and neuroticism. That is, the researchers predicted that a person's smoking habits would depend on the combination of which version of the gene a person had and the results of a 240-item personality questionnaire.

No link between conscientiousness and cigarettes

The interaction between the gene and neuroticism was significant in people with the short variant and high levels of neuroticism. People in this group were no more likely to begin smoking than others in the study. However, if they start, it is harder for them to quit, according to the data published in the latest issue of Molecular Psychiatry.

To verify their result, the researchers looked for interactions between the short and long gene variants and a different personality trait altogether—conscientiousness—and found no connection to smoking.

Before submitting their paper for publication, Hamer's team shared the findings with Caryn Lerman at Georgetown University Medical Center. She and her colleagues then tried to reproduce the result in a group of 185 smokers. The researchers found an association between neuroticism and smoking in people with the short—but not the long—form of the serotonin transporter gene. This study is also published in Molecular Psychiatry.

The clinical implications of these findings could be in the selection of effective smoking cessation drugs and strategies for individuals. "The molecular genetic analysis of the psychiatric diagnoses of nicotine dependence and withdrawal is at an early stage," the authors of the first study write. "We hope this report will stimulate further research in this area."

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Hu, S. et al. Interaction between the serotonin transporter gene and neuroticism in cigarette smoking behavior. Mol Psychiatry 5, 181-188 (March 2000).
Lerman, C. et al. Interacting effects of the serotonin transporter gene and neuroticism in smoking practices and nicotine dependence. Mol Psychiatry 5, 189-192 (March 2000).

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