Significant associations of CHRNA2 and CHRNA6 with nicotine dependence in European American and African American populations.

The direct physiological effects that promote nicotine dependence (ND) are mediated by nicotinic acetylcholine receptors (nAChRs). In line with the genetic and pharmacological basis of addiction, many previous studies have revealed significant associations between variants in the nAChR subunit genes and various measures of ND in different ethnic samples. In this study, we first examined the association of variants in nAChR subunits α2 (CHRNA2) and α6 (CHRNA6) genes on chromosome 8 with ND using a family sample consisting of 1,730 European Americans (EAs) from 495 families and 1,892 African Americans (AAs) from 424 families (defined as the discovery family sample). ND was assessed by two standard quantitative measures: smoking quantity (SQ) and the Fagerström Test for ND (FTND). We found nominal associations for all seven tested SNPs of the genes with at least one ND measure in the EA sample and for two SNPs in CHRNA2 in the AA sample. Of these, associations of SNPs rs3735757 with FTND (P = 0.0068) and rs2472553 with both ND measures (with a P value of 0.0043 and 0.00086 for SQ and FTND, respectively) continued to be significant in the EA sample even after correction for multiple tests. Further, we found several haplotypes that were significantly associated with ND in the EA sample in CHRNA6 and in the both EA and AA samples in CHRNA2. To confirm the associations of the two genes with ND, we conducted a replication study with an independent case-control sample from the SAGE study, which showed a significant association of the two genes with ND, although the significantly associated SNPs were not always the same in the two samples. Together, these findings indicate that both CHRNA2 and CHRNA6 play a significant role in the etiology of ND in AA and EA smokers. Further replication in additional independent samples is warranted.

Severity of withdrawal symptomatology in follicular versus luteal quitters: The combined effects of menstrual phase and withdrawal on smoking cessation outcome.

Women are at an increased risk of relapse after a smoking cessation attempt. While the reasons for this phenomenon are not fully understood, recent research indicates that both the menstrual cycle and negative symptomatology may play a role. The goal of this study was to describe the association between withdrawal symptoms during attempted smoking cessation, and to investigate the impact of these symptoms on smoking cessation outcomes as defined by 7-day point prevalence at 14 and 30 days. Negative symptoms associated with the premenstrual period were also assessed. Participants (n = 202) were 29.8 (SD +/- 6.6) years old and smoked 16.6 (SD +/- 5.6) cigarettes per day. They were randomly assigned to quit smoking in the follicular (n = 106) or luteal (n = 96) menstrual phase. We observed several significantly more severe premenstrual and withdrawal symptoms in the luteal phase. Regardless of quit phase, most withdrawal symptoms were associated with an increased risk of relapse at 14 and 30 days post quit date. Participants attempting to quit smoking in the follicular phase who had higher levels of Anger and Craving were more likely to relapse to smoking at 14-days (OR = 2.00, p-value = 0.026; OR = 2.63, p-value = 0.006; respectively). These data suggest that the menstrual cycle may play a role in smoking cessation outcome, as well as in the symptomatology experienced during a cessation attempt.

Substance use, trait measures, and subjective response to nicotine in never-smokers stratified on parental smoking history and sex.

INTRODUCTION: Male and female never-smokers stratified on parental history of smoking were tested for possible differences in susceptibility to the hedonic effects of nicotine. METHODS: We recruited nicotine-exposed never-smokers with two never-smoking biological parents (PH-) or two ever-smoking biological parents (PH+). After completing a baseline assessment battery focusing on conditions or behaviors associated with smoking, participants were tested for subjective and hedonic effects in response to administration of three different nicotine doses (0.0, 0.5, and 1.0 mg) via nasal spray. Physiological and biochemical reactivity also was monitored. RESULTS: PH+ were significantly more likely to report having experienced a "buzz" upon early smoking experimentation and to have histories of alcohol abuse and alcoholism; they also scored higher on disordered eating. In response to nicotine dosing, PH+ reported an increase in depressed mood, compared with a minimal response in PH-, in keeping with our expectation that nicotine would have more pronounced effects in PH+. Regardless of parental history, women reported experiencing greater anxiety in response to the highest nicotine dose, compared with men. DISCUSSION: Further exploration in larger samples, using more stringent selection criteria, a wider range of measures, and a less aversive dosing method, may provide a full test of the possible utility of the parental history model for illuminating biobehavioral mechanisms underlying response to nicotine. Also important would be broadening the scope of inquiry to include comparisons with ever-smokers to determine what protected PH+ from becoming smokers, despite the presence of factors that might be expected to decrease resilience and increase susceptibility.

Race differences in factors relating to smoking initiation.

To investigate race differences in retrospectively-reported early smoking experiences, we studied African-American (n=48) and Caucasian (n=155) current smokers who participated in a study designed to identify phenotypic and genotypic factors associated with smoking. Compared with Caucasian smokers, African-American smokers were less educated (mean+/-s.e.m.: 13.3+/-0.25 vs. 14.3 +/- 0.16; p<.01), had higher BMI (28.9+/-1.06 vs. 26.7+/-0.52; p<.05), and smoked significantly fewer cigarettes/day (14.1+/-1.00 vs. 18.4+/-0.74; p<.01). Ninety percent of African-American smokers consumed menthol cigarettes, as opposed to 25% of Caucasian smokers. African-American smokers were significantly older than Caucasian smokers upon initial smoking experimentation (17.4+/-1.1 vs. 14.7+/-0.3; p<.05) and onset of regular smoking (19.7+/-0.9 vs. 17.4+/-0.4; p<.05). African-American smokers were significantly more likely than Caucasian smokers to endorse global pleasurable sensations (48% vs. 30%; p<.05), "pleasurable rush or buzz" (62% vs. 43%; p<.05), and "relaxing" (45% vs. 27%; p<.05) as early experiences with smoking, whereas Caucasian smokers were marginally more likely to report dizziness and difficulty inhaling (61% vs. 45%; p<.10 and 48% vs. 31%; p<.10, respectively). Caucasian smokers were significantly more likely to endorse friends (6.9+/-0.2 vs. 4.8+/-0.4; p<.0001) and "perk me up" (4.2+/-0.3 vs. 3.1+/-0.4; p<.05) and marginally more likely to endorse buzz (4.2+/-0.2 vs. 3.4+/-0.5; p<.10) as reasons for starting to smoke. Further research is needed to determine the relative contributions of genetic, developmental, and socio-cultural factors to these findings.

Using MIMIC models to examine the relationship between current smoking and early smoking experiences.

INTRODUCTION: The present study expands previous research on early experiences with tobacco by using a Multiple Indicator Multiple Causes (MIMIC) model, which permits combining indicators tapping into pleasant experiences into one latent construct and those indicators of unpleasant experiences into another latent construct. METHODS: A sample of 458 participants was recruited via newspaper advertisements. Response to early experimentation with cigarettes was assessed using the Early Smoking Experiences questionnaire, in which participants were asked the following question: "The first time you tried cigarettes, did you experience any of the following? (pleasurable and displeasurable sensations [overall], pleasurable rush or buzz, dizziness, relaxation, nausea, cough, difficulty inhaling)." These experiences were rated on a scale ranging from 1 = none to 4 = intense. RESULTS: The MIMIC model revealed that current smoking status and age of initial experimentation with cigarettes were significantly associated with both early pleasant and unpleasant experiences (p < .05). African Americans were less likely than Whites to have early unpleasant experiences (p < .05). No association was found between race and early pleasant experiences. DISCUSSION: Our findings are consistent with the inferences that pleasant experiences in response to early experimentation with smoking lead to regular smoking and that positive experiences play a stronger role than negative experiences in the transition to regular smoking. Our study also demonstrates that the MIMIC model is pertinent and practicable in nicotine and smoking research. We recommend it as a useful tool for identifying endophenotypes related to nicotine dependence and tobacco use latent constructs.

Never-smokers with a positive family smoking history are more likely to be overweight or obese than never-smokers with a negative family smoking history.

To shed light on the complex relationship between smoking and body weight, we used never-smokers stratified on family smoking history to model the effects of a diathesis for smoking on body weight without the potential confound of metabolic changes or decreased physical activity caused by chronic tobacco smoke exposure. Participants were 100 family history negative never-smokers (FH-; 2 never-smoking parents) and 71 family history positive never-smokers (FH+; 2 ever-smoking parents). Controlling for significant group differences in race and age, BMI was significantly higher in FH+ (26.7+/-.6) than in FH- (24.5+/-.4; F=10.351 p<.01). Further analysis using logistic regression showed that FH+ were 2.7 times as likely to be overweight/obese (BMI > or = 25; 95% C.I. 1.398-5.351; p<.01). FH+ scored significantly higher on the Dieting and Bingeing Severity Scale than FH- and were significantly more likely to score in the severe or at-risk range. FH+ drank significantly more alcohol than FH-; they scored significantly higher on the CAGE and on the Michigan Alcohol Screening Test. Our analyses provide support for the role of inherited and/or environmentally-driven tendencies towards disinhibited eating and/or risky behaviors in general in the observed differences in BMI. No group differences in BMI or likelihood of being overweight/obese emerged based on prenatal exposure to nicotine in FH+ smokers, although our sample was too small to rule out an association. Further research in larger samples, using more complex statistical models, will be needed to disentangle these issues and identify causal pathways.

Influence of phase-related variability in premenstrual symptomatology, mood, smoking withdrawal, and smoking behavior during ad libitum smoking, on smoking cessation outcome.

Emerging evidence suggests that women have a more difficult time quitting smoking than men-possibly due, in part, to sex hormones. The present study characterized mood, premenstrual symptomatology, and smoking withdrawal, as well as smoking behavior, in the follicular and luteal phases during ad libitum smoking in 25 women intending to quit. We also investigated the possible influence of phase-related variability in these measures on likelihood of study adherence and smoking cessation. We found that premenstrual symptomatology, as well as some measures of mood and smoking withdrawal, were significantly higher during the luteal phase than in the follicular phase. Cigarettes/day did not vary by menstrual cycle phase. Phase-related variability in premenstrual symptomatology [F(3, 20)=2.82, p=0.0650)] and urge to smoke [F(2, 21)=4.85, p=0.0186)] were associated with relapse. These data support the inference that sex hormones influence smoking cessation outcome. This knowledge may contribute to the development of more rational and effective smoking cessation interventions for women.

Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with 'pleasurable buzz' during early experimentation with smoking.

AIMS: To extend the previously identified association between a single nucleotide polymorphism (SNP) in neuronal acetylcholine receptor subunit alpha-5 (CHRNA5) and nicotine dependence to current smoking and initial smoking-experience phenotypes. DESIGN, SETTING, PARTICIPANTS: Case-control association study with a community-based sample, comprising 363 Caucasians and 72 African Americans (203 cases, 232 controls). MEASUREMENTS: Cases had smoked > or = five cigarettes/day for > or = 5 years and had smoked at their current rate for the past 6 months. Controls had smoked between one and 100 cigarettes in their life-time, but never regularly. Participants also rated, retrospectively, pleasurable and displeasurable sensations experienced when they first smoked. We tested for associations between smoking phenotypes and the top 25 SNPs tested for association with nicotine dependence in a previous study. FINDINGS: A non-synonymous coding SNP in CHRNA5, rs16969968, was associated with case status [odds ratio (OR) = 1.5, P = 0.01] and, in Caucasians, with experiencing a pleasurable rush or buzz during the first cigarette (OR = 1.6, P = 0.01); these sensations were associated highly with current smoking (OR = 8.2, P = 0.0001). CONCLUSIONS: We replicated the observation that the minor allele of rs16969968 affects smoking behavior, and extended these findings to sensitivity to smoking effects upon experimentation. While the ability to test genetic associations was limited by sample size, the polymorphism in the CHRNA5 subunit was shown to be associated significantly with enhanced pleasurable responses to initial cigarettes in regular smokers in an a priori test. The findings suggest that phenotypes related to subjective experiences upon smoking experimentation may mediate the development of nicotine dependence.

Validity and reliability of the Weight Control Smoking Scale.

The Weight Control Smoking Scale (WCSS), originally developed as part of a Reasons for Smoking Scale, includes 3 items (smoke to avoid weight gain; smoke to control appetite; less hungry when smoking). Although widely used, it has not previously been subjected to psychometric analysis. To fill this gap, we analyzed data from 1512 smokers. WCSS score correlated significantly and positively with the Dieting and Bingeing Severity Scale, self-efficacy about relapse if postcessation weight gain occurred, increased appetite/weight gain as a withdrawal symptom, and the Three Factor Eating Questionnaire subscales, and negatively with Body Satisfaction. Cronbach's alpha was .834. Female participants scored significantly higher than males. When only Black and White smokers were included, a significant interaction emerged such that White women scored higher than any other category. In a subsample of 50 smokers who completed the questionnaire twice, test-retest correlations were significant for all items and for the scale as a whole. Overall, our results suggest that the WCSS is a reliable and valid instrument that lends itself to use as a screening tool.

Association of withdrawal features with nicotine dependence as measured by the Fagerström Test for Nicotine Dependence (FTND).

The aim of this study was to advance our understanding of how nicotine dependence level, defined by the Fagerström Test of Nicotine Dependence (FTND), relates to nicotine withdrawal features. We classified nicotine dependence in two categories, 1) low dependence (LD; FTND<4) and 2) high dependence (HD; FTND> or =4). A sample of 241 smokers was recruited via newspaper ads and public notices. Using a multivariate response model with adjustments for age, sex, age at first cigarette, race, and current or lifetime depression, we observed a small to modest statistically robust association between nicotine dependence level and withdrawal features such as, irritation/anger (adjusted relative risk, aRR=1.2; 95% CI 1.0, 1.3); nervousness (aRR=1.3; 95% CI 1.1, 1.6); restlessness (aRR=1.2; 95% CI 1.1, 1.4); difficulty concentrating (aRR=1.3; 95% CI 1.1, 1.7); and trouble sleeping (aRR=1.8; 95% CI 1.2, 2.6). Our findings are consistent with the inference that the FTND measures "physiological dependence" and that multidimensional approaches are needed to capture the full range of smoking phenotypology.

Web-based smoking-cessation programs: results of a randomized trial.

BACKGROUND: Initial trials of web-based smoking-cessation programs have generally been promising. The active components of these programs, however, are not well understood. This study aimed to (1) identify active psychosocial and communication components of a web-based smoking-cessation intervention and (2) examine the impact of increasing the tailoring depth on smoking cessation. DESIGN: Randomized fractional factorial design. SETTING: Two HMOs: Group Health in Washington State and Henry Ford Health System in Michigan. PARTICIPANTS: 1866 smokers. INTERVENTION: A web-based smoking-cessation program plus nicotine patch. Five components of the intervention were randomized using a fractional factorial design: high- versus low-depth tailored success story, outcome expectation, and efficacy expectation messages; high- versus low-personalized source; and multiple versus single exposure to the intervention components. MEASUREMENTS: Primary outcome was 7 day point-prevalence abstinence at the 6-month follow-up. FINDINGS: Abstinence was most influenced by high-depth tailored success stories and a high-personalized message source. The cumulative assignment of the three tailoring depth factors also resulted in increasing the rates of 6-month cessation, demonstrating an effect of tailoring depth. CONCLUSIONS: The study identified relevant components of smoking-cessation interventions that should be generalizable to other cessation interventions. The study also demonstrated the importance of higher-depth tailoring in smoking-cessation programs. Finally, the use of a novel fractional factorial design allowed efficient examination of the study aims. The rapidly changing interfaces, software, and capabilities of eHealth are likely to require such dynamic experimental approaches to intervention discovery.

Favorite cigarette of the day in a random sample of women smokers.

From a random digit dialing survey of American women, we assessed current smokers (n=371). Respondents were 33.6+/-7.6 years old, 49.6% married, and 87.6% White, with an FTND score of 3.9+/-2.6. When asked "which cigarette of the day would be the most difficult for you to give up?" 30 women gave uncodable responses and 341 women provided answers subsequently coded into 5 categories: FIRST; 43.7%, MEAL; 29.3%, LAST; 13.8%, ROUTINE; 7.3%, and ENHANCE; 5.9%. Response groups differed significantly on age (p<.01), smoking rate (p<.001), time to first cigarette (p<.001), and self-rated health (p<.05). In post hoc analyses, FIRST were older, smoked more cigarettes/day, and smoked sooner after waking than at least one other group. LAST smoked the fewest cigarettes/day, and ENHANCE rated their health significantly better than did all other groups. The FTND is coded as 1 for "first" and 0 for any other response. Examining more closely the richness contained in that "other" category is a novel approach that may prove useful as a phenotyping tool.

Genome-wide linkage analysis for smoking-related regions, with replication in two ethnically diverse populations.

As part of the Genetic Epidemiology Network of Arteriopathy, hypertensive sibships were collected and smoking behavior recorded. Using an affected sibpair design and genome-wide microsatellite data markers ( approximately 10 cM coverage), we identified 214 non-Hispanic White sibships (502 sibpairs) from Rochester, Minnesota (M (age) [SD] = 55.68 years [10.56]) and 206 Black sibships (376 sibpairs) from Jackson, Mississippi (M (age) = 57.97 [8.94]), who had smoked for at least 3 years, and performed nonparametric linkage analysis using GENEHUNTER. We found evidence of linkage on chromosome 3 in both Whites (LOD = 1.76@109 cM) and Blacks (LOD = 2.03@122 cM). Each of these peaks had a secondary smaller peak at 140-147 cM that was statistically suggestive only in the Black sample (LOD = 1.4). The peak for the combined samples was suggestive of strong linkage (LOD = 3.24@124 cM). Additional suggestive peaks (LOD>1.3) were found in the White (chromosomes 8 [26 cM] and 19 [36 cM]) and Black sibships (chromosome 10 [153 cM]) but did not overlap with corresponding regions in the other ethnic group. This is the first study to identify a chromosomal region that has replicate evidence of linkage to smoking in two independent samples of similar size differing both geographically and ethnically. The gene for serotonin receptor 1F (HTR1F) is located in the region of the chromosome 3 linkage signal, representing at least one potential candidate gene. Fine mapping may well provide useful new information about genetic factors underlying nicotine dependence.

Evaluating the ability of visual images to inform college women about the link between smoking and cervical intraepithelial neoplasia (CIN) and to motivate quitting: critical dimensions.

BACKGROUND: Because cervical intraepithelial neoplasia (CIN, or dysplasia) is associated with behavioral factors, health education is an important part of the care of patients at risk for this disease. Smoking, which is strongly associated with CIN and cancers, is particularly important because smoking cessation, even after the onset of CIN, improves outcomes. This study is part of an effort to identify effective ways to convey information about the association between smoking and CIN to at-risk women. METHODS: We created 8 images to systematically incorporate a range of artistic approaches to inform viewers about the relationship between smoking and CIN. College women smokers were recruited to participate. Participants rated the images on the extent to which they attracted attention and motivated smoking cessation. RESULTS: Significant differences were identified in the response of this population to visual images differing in content and style. Informative images were more compelling than those that were emotive. CONCLUSIONS: Further exploration is warranted to improve our understanding of how visual forms of health education can impact smoking cessation by those at risk for cervical cancer.

Differences in smoking patterns among women smokers with childhood versus later onset of weight problems.

We hypothesized that among overweight women smokers, those with Childhood Onset weight problems may be more likely to engage in unhealthy eating and dieting behaviors, including smoking to control weight. Data were collapsed from 89 currently overweight (BMI> or =25) women smokers who were recruited to participate in smoking research projects that focused on weight, body image, and food intake. We compared those who reported first becoming overweight before Junior High School (n=22) with those who recalled first experiencing weight problems during Junior High School or later (n=67). Women with Childhood Onset weight problems reported first trying cigarettes at a significantly younger age than those with Later Onset (13 vs. 15 years of age, respectively), and they reported more nicotine withdrawal symptoms during smoking abstinence, with a significantly greater likelihood of endorsing anger/irritability and trouble concentrating. No group differences were evident for cigarettes per day or other indicators of nicotine dependence (e.g., FTND). Although it is unclear whether having weight problems during childhood contributes directly to smoking initiation, our results provide evidence that Childhood Onset weight problems may serve as a marker for earlier smoking experimentation and may also complicate cessation efforts due to their association with elevated withdrawal symptomatology. Future longitudinal studies with prospective measures of weight, dieting, and smoking initiation may be helpful in establishing causal pathways in different subgroups of smokers.

Actual versus perceived risk of cervical cancer among college women smokers.

UNLABELLED: Cervical cancer is a well-established smoking-related illness, but many at-risk women are unaware of this link. OBJECTIVE: The authors designed this study to (1) investigate the relationship of smoking behavior with the history of abnormal Pap test results, sexual history, and perceived risk of cervical cancer and (2) determine whether self-classified smoking status (and hence perceived risk) corresponds with actual smoking behavior in a college student population. PARTICIPANTS AND METHOD SUMMARY: College women students (N = 135) completed a survey assessing smoking history, health history, sexual risk behavior, and risk awareness. RESULTS: Relative to those who had not smoked in the past month, current smokers (n = 36, or 27% of the total sample) perceived themselves to be at higher risk for developing cervical cancer, but did not demonstrate increased awareness of specific cervical cancer risk factors, including smoking. Twenty-eight percent (10 of 36) of past-month smokers did not define themselves as current smokers. CONCLUSION: The authors conclude that anti-smoking and health-related messages targeting smokers may misfire for individuals who do not define themselves as smokers but are nonetheless at risk for smoking-related consequences and escalating use.

Body image, body satisfaction, and eating patterns in normal-weight and overweight/obese women current smokers and never-smokers.

To explore differences between women smokers and never-smokers in body image and eating patterns, we analyzed data obtained from 587 women (18-55 years old) recruited to participate in laboratory investigations not focused on weight concerns. The sample consisted of 420 current smokers and 167 never-smokers; 44% of each group were overweight or obese (BMI>or=25). Questionnaires included measures of body image, body dissatisfaction, and restrained and disinhibited eating. Smokers did not differ from never-smokers on perceived body shape but endorsed a thinner preferred body shape and scored lower on body satisfaction than never-smokers. Smokers also scored higher on measures of disinhibited eating. Among smokers, those who were overweight/obese scored higher than normal-weight smokers on concerns about post-cessation weight gain and lower on self-efficacy to avoid relapse if weight increased. Our findings suggest that women smokers may require help in attaining a more realistic body image and attention to dysfunctional eating patterns if they are to achieve and maintain a healthful weight and/or to quit smoking successfully. They also indicate that overweight smokers may be at elevated risk of relapse in the face of post-cessation weight gain.

Differences in smoking-related variables based on phenylthiocarbamide "taster" status.

Test strips impregnated with phenylthiocarbamide (PTC) have been used to identify genetic differences based on whether a bitter taste is perceived. To determine whether smokers who perceive PTC as bitter tasting ("tasters") would differ from those who describe it as tasteless ("non-tasters") on smoking-related variables, we studied 464 current smokers (70% female, 79% White; mean age 30.5+/-9 years) recruited to participate in laboratory experiments and clinical trials. Of these, 217 (47%) reported the PTC strips as tasteless and 154 (33%) as tasting bitter. The remaining 93 (20%) described the taste as salty, sweet, or other and were excluded from further analyses. Comparing tasters with non-tasters, we found significant differences in mean (S.D.) total years smoked (14.5 [9.2] for non-tasters, vs. 12.6 [8.4] for tasters, p<.05), Fagerstrom Tolerance Questionnaire scores (6.4 [2.1] vs. 5.8 [2.1], p<.01), and scores on the Positive Reinforcement scale of the Michigan-Nicotine Reinforcement Questionnaire (8.1 [2.9] vs. 6.8 [3.1], p<.05). Results suggest that among smokers, ability to taste PTC may confer some protection from development of nicotine dependence and positive reinforcement from smoking.

Unaided smoking cessation among smokers in treatment for alcohol dependence.

To investigate the possible impact of treatment of alcohol dependence on smoking, we studied 144 smokers in an alcohol treatment center for whom 6-month data were available. Of those, 18 reported not smoking at 6 months. No significant differences in age, gender, or race were observed between quitters and continuing smokers. Quitters at 6 months were significantly more likely to be low dependent smokers than were continuing smokers and were significantly more likely to report no drinking during the past 28 days at the end of 1 month's treatment (93%) than continuing smokers (62%). These findings suggest that quitting smoking may be associated with low levels of nicotine dependence and favorable alcohol treatment response in alcoholic smokers.