Genetic predictors of cue- and stress-induced cigarette craving: an exploratory study

Cigarette cravings in response to environmental cues and stressors are widely recognized as important predictors of smoking cessation outcomes. Accumulating evidence suggests that genetics plays a role in these craving responses, as well as in smoking cessation more generally. Previous studies of genetic polymorphisms have been limited by examination of single candidate genes and the use of broadly defined phenotypes (e.g., smoking history). In addition, research examining the similarities and differences between cue- and stress-induced cravings has been limited, although some evidence has suggested that they may have common genetic underpinnings. In the current study, we examined associations between a panel of 1,350 candidate genetic polymorphisms and craving responses to laboratory smoking cues and stressors. We hypothesized that common genetic polymorphisms would be predictive of both cue- and stress-induced craving. Nicotine-dependent smokers (n = 210) donated a blood sample, were exposed to neutral, smoking-related, and stress-related stimuli, and completed craving questionnaires immediately prior to and following each stimulus. Findings indicated that craving responses to smoking cues and stressors were moderately correlated (r = .44). However, genetic analysis revealed that cue and stress-induced cigarette craving were predicted by different polymorphisms, such that variants in the glycine and dopamine pathways were predictive of cue-induced craving, whereas variants in the stress-corticotropin pathway predicted stress-induced craving.

Study results provide no support for the hypothesis that cue- and stress-induced craving have the same genetic predictors.