Dataset Information

Association between nicotine dependence severity, BOLD response to smoking cues, and functional connectivity.

ABSTRACT: Enhanced motivational salience towards smoking cues is a consequence of chronic nicotine use, but the degree to which this value increases beyond that of other appetitive cues is unknown. In addition, it is unclear how connectivity between brain regions influences cue reactivity and how cue reactivity and functional connectivity are related to nicotine dependence severity. This study examined neural responses during the presentation of smoking cues and appetitive control cues, as well as functional connectivity in 116 smokers with a range of nicotine dependence severity. Smoking cues elicited greater response above baseline than food cues in orbitofrontal cortex (OFC) and supplementary motor area (SMA) and less deactivation below baseline in middle frontal gyrus, inferior parietal lobe, and middle temporal gyrus. Psychophysiological interaction (PPI) analysis using right OFC as a seed revealed increased connectivity with somatosensory cortex and lateral inferior parietal lobe during smoking cues compared with food cues. Similarly, a PPI analysis using left insula as a seed showed stronger connectivity with somatosensory cortex, right insula, OFC, and striatum. Finally, relationships with nicotine dependence scores showed enhanced response in insula and dorsal anterior cingulate cortex in the smoking vs food comparison, and increased connectivity between insula and circuits involved in motivated behavior. Combined, these results suggest that smokers engage attentional networks and default mode networks involved in self-referential processing to a greater degree during smoking cues. In addition, individuals with greater nicotine dependence severity show increased engagement of sensorimotor and motor preparation circuits, suggesting increased reliance on habitual behavior.

SUBMITTER: Claus ED

PROVIDER: S-EPMC3799055 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Association between nicotine dependence severity, BOLD response to smoking cues, and functional connectivity.

Claus Eric D ED Blaine Sara K SK Filbey Francesca M FM Mayer Andrew R AR Hutchison Kent E KE

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20130524 12

Enhanced motivational salience towards smoking cues is a consequence of chronic nicotine use, but the degree to which this value increases beyond that of other appetitive cues is unknown. In addition, it is unclear how connectivity between brain regions influences cue reactivity and how cue reactivity and functional connectivity are related to nicotine dependence severity. This study examined neural responses during the presentation of smoking cues and appetitive control cues, as well as functio ...[more]

PMID: 23708507

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Project description:IntroductionGenetic variation in Cytochrome P450 2A6 (CYP2A6), the major nicotine metabolizing enzyme, is associated with nicotine dependence and smoking cessation. Nicotine dependence severity also predicts smoking cessation. Our goals were to determine how CYP2A6 variation and nicotine dependence alter smoking cessation, and whether dependence could refine CYP2A6-based treatment recommendations.Aims and methodsAdult smokers treated for 12 weeks with placebo, nicotine patch, or varenicline (NCT01314001) were grouped as CYP2A6 normal (n = 567) or slow (n = 432) nicotine metabolizers based on a CYP2A6 weighted genetic risk score. Fagerström test for nicotine dependence scores were measured at baseline and biochemically verified smoking cessation was assessed at end of treatment.ResultsDependence neither mediated nor moderated an association between CYP2A6 variation and smoking cessation overall, within any treatment arm, or after stratifying by ancestry (n = 591 European, n = 408 African ancestry) or sex (n = 444 women, n = 555 men). In within-treatment analyses, the mediation effect odds ratio (OR) ranged from 0.95 to 1.00 and the bias-corrected 95% confidence interval contained 1. Moderation (i.e. interaction) effect ORs ranged from 0.88 to 1.61 (p = .397-.828). For CYP2A6 normal metabolizers, quit rates on varenicline were similar for those with high (41.1%) and low (43.4%) dependence, while quit rates were lower for those with high versus low dependence on both patch (16.5 vs. 29.7%) and placebo (8.9 vs. 18.5%). CYP2A6 slow metabolizers with high versus low dependence had lower quit rates in all three treatment arms.ConclusionsAlthough nicotine dependence severity neither mediated nor moderated CYP2A6 associations with smoking cessation, incorporating information on dependence may optimize the choice of smoking cessation treatment aid in CYP2A6 normal and slow metabolizers.ImplicationsVariation in CYP2A6 and nicotine dependence severity alter smoking cessation success. Our findings suggest that while nicotine dependence severity is unlikely to mediate or moderate CYP2A6 associations with cessation, incorporating patient information on both CYP2A6 and nicotine dependence severity may lead to improved smoking cessation strategies.

Project description:IntroductionThe nicotine metabolite ratio and nicotine equivalents are measures of metabolism rate and intake. Genome-wide prediction of these nicotine biomarkers in multiethnic samples will enable tobacco-related biomarker, behavioral, and exposure research in studies without measured biomarkers.Aims and methodsWe screened genetic variants genome-wide using marginal scans and applied statistical learning algorithms on top-ranked genetic variants, age, ethnicity and sex, and, in additional modeling, cigarettes per day (CPD), (in additional modeling) to build prediction models for the urinary nicotine metabolite ratio (uNMR) and creatinine-standardized total nicotine equivalents (TNE) in 2239 current cigarette smokers in five ethnic groups. We predicted these nicotine biomarkers using model ensembles and evaluated external validity using dependence measures in 1864 treatment-seeking smokers in two ethnic groups.ResultsThe genomic regions with the most selected and included variants for measured biomarkers were chr19q13.2 (uNMR, without and with CPD) and chr15q25.1 and chr10q25.3 (TNE, without and with CPD). We observed ensemble correlations between measured and predicted biomarker values for the uNMR and TNE without (with CPD) of 0.67 (0.68) and 0.65 (0.72) in the training sample. We observed inconsistency in penalized regression models of TNE (with CPD) with fewer variants at chr15q25.1 selected and included. In treatment-seeking smokers, predicted uNMR (without CPD) was significantly associated with CPD and predicted TNE (without CPD) with CPD, time-to-first-cigarette, and Fagerström total score.ConclusionsNicotine metabolites, genome-wide data, and statistical learning approaches developed novel robust predictive models for urinary nicotine biomarkers in multiple ethnic groups. Predicted biomarker associations helped define genetically influenced components of nicotine dependence.ImplicationsWe demonstrate development of robust models and multiethnic prediction of the uNMR and TNE using statistical and machine learning approaches. Variants included in trained models for nicotine biomarkers include top-ranked variants in multiethnic genome-wide studies of smoking behavior, nicotine metabolites, and related disease. Association of the two predicted nicotine biomarkers with Fagerström Test for Nicotine Dependence items supports models of nicotine biomarkers as predictors of physical dependence and nicotine exposure. Predicted nicotine biomarkers may facilitate tobacco-related disease and treatment research in samples with genomic data and limited nicotine metabolite or tobacco exposure data.

Dataset Information

Association between nicotine dependence severity, BOLD response to smoking cues, and functional connectivity.

Publications

Association between nicotine dependence severity, BOLD response to smoking cues, and functional connectivity.

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