Initial sensitivity to substances may affect patterns of future use and dependence. Because smoking and alcohol use are strongly linked, because animal studies indicate cross-sensitivity, and because ...genetic determinants of nicotine and alcohol dependence overlap, we studied the relationships between retrospectively reported responses to both substances in current smokers (
n=111) and never-smokers (
n=86). Early smoking experiences were correlated with comparable responses to alcohol in smokers, and to a lesser extent, in never-smokers. Both pleasurable early experiences with nicotine and pleasurable experiences with alcohol predicted current alcohol intake; pleasurable early experiences with alcohol also predicted alcohol dependence. Neither pleasurable nor displeasurable experiences with either substance predicted current amount smoked or degree of nicotine dependence. These preliminary findings may have implications for understanding the mechanisms underlying the smoking–alcohol link.
Objective:
A recent study provisionally identified numerous genetic variants as risk factors for the transition from smoking to the development of nicotine dependence, including an amino acid change ...in the 5 nicotinic cholinergic receptor (
CHRNA5
). The purpose of this study was to replicate these findings in an independent data set and more thoroughly investigate the role of genetic variation in the cluster of physically linked nicotinic receptors,
CHRNA5-CHRNA3-CHRNB4
, and the risk of smoking.
Method:
Individuals from 219 European American families (N=2,284) were genotyped across this gene cluster to test the genetic association with smoking. The frequency of the amino acid variant (rs16969968) was studied in 995 individuals from diverse ethnic populations. In vitro studies were performed to directly test whether the amino acid variant in the CHRNA5 influences receptor function.
Results:
A genetic variant marking an amino acid change showed association with the smoking phenotype (p=0.007). This variant is within a highly conserved region across nonhuman species, but its frequency varied across human populations (0% in African populations to 37% in European populations). Furthermore, functional studies demonstrated that the risk allele decreased response to a nicotine agonist. A second independent finding was seen at rs578776 (p=0.003), and the functional significance of this association remains unknown.
Conclusions:
This study confirms that at least two independent variants in this nicotinic receptor gene cluster contribute to the development of habitual smoking in some populations, and it underscores the importance of multiple genetic variants contributing to the development of common diseases in various populations.
Nicotine dependence is one of the world's leading causes of preventable death. To discover genetic variants that influence risk for nicotine dependence, we targeted over 300 candidate genes and ...analyzed 3713 single nucleotide polymorphisms (SNPs) in 1050 cases and 879 controls. The Fagerström test for nicotine dependence (FTND) was used to assess dependence, in which cases were required to have an FTND of 4 or more. The control criterion was strict: control subjects must have smoked at least 100 cigarettes in their lifetimes and had an FTND of 0 during the heaviest period of smoking. After correcting for multiple testing by controlling the false discovery rate, several cholinergic nicotinic receptor genes dominated the top signals. The strongest association was from an SNP representing CHRNB3, the β3 nicotinic receptor subunit gene (P = 9.4 × 10−5). Biologically, the most compelling evidence for a risk variant came from a non-synonymous SNP in the α5 nicotinic receptor subunit gene CHRNA5 (P = 6.4 × 10−4). This SNP exhibited evidence of a recessive mode of inheritance, resulting in individuals having a 2-fold increase in risk of developing nicotine dependence once exposed to cigarette smoking. Other genes among the top signals were KCNJ6 and GABRA4. This study represents one of the most powerful and extensive studies of nicotine dependence to date and has found novel risk loci that require confirmation by replication studies.
A conference on the conduct of genomic research on complex behaviors was convened at the University of Michigan to demystify genetic research by describing the tools and methodologies for identifying ...genes and to assess the feasibility of conducting genomic research on smoking, a complex behavior with major public health import. These proceedings are excerpts based on the presentations at the conference.
This article is a brief history of the Society for Research on Nicotine and Tobacco, now in its 10th year. During its first decade, the Society grew from around 100 to over 900 members, sponsored ...well-attended annual meetings and highly influential satellite conferences to promote research, provided timely electronic and print services to increase the flow of information, and founded a new journal to facilitate communication of scientific advances. These accomplishments highlight the progress that has been made in meeting the objective of the Society to stimulate new knowledge about nicotine in all its manifestations.
Web-Based Smoking-Cessation Programs Strecher, Victor J., PhD; McClure, Jennifer B., PhD; Alexander, Gwen L., PhD ...
American journal of preventive medicine,
2008, Volume:
34, Issue:
5
Journal Article
Peer reviewed
Open access
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.
We investigated whether 52 same-sex sibling pairs discordant for ever-smoking differed on psychiatric cofactors, alcohol and caffeine use, and responses to initial exposure to smoking. Ever-smokers ...scored significantly higher on measures of novelty seeking, depression, and childhood ADHD, and on alcohol dependence, alcohol intake, and caffeine intake. They reported significantly more pleasurable experiences, dizziness, “buzz,” and relaxation upon initial exposure to smoking and significantly fewer displeasurable sensations, nausea, and cough than did nicotine-exposed, never-smoking siblings. Ever-smokers had significantly fewer years of education than their never-smoking siblings, suggesting that the concentration of smokers in lower socioeconomic strata may be partly due to downward mobility among smokers, possibly because of the observed elevation in psychiatric cofactors, which may interfere with academic performance. These findings are consistent with differences previously identified in unrelated ever- and never-smokers. Because same-sex siblings typically share a large set of common environments during childhood, our findings could be due either to genetic differences among siblings and/or (excepting educational level and responses to early exposure) to differences in adult environments.
Although investigators have used family history methods to investigate familial clustering of disorders such as depressive disorder, alcoholism, coronary heart disease, and cancer, research of this ...type is relatively new to the field of smoking. We examined agreement between proband report of parental smoking behavior and parent's self-reported smoking behavior in 126 proband–parent pairs. Probands were either never, current, or exsmokers; parents were either current or exsmokers. Agreement between proband and parent was better for smoking behaviors when the parent was a current smoker. We found good proband–parent agreement for some smoking behaviors when the parent was a current smoker (e.g., age started smoking mean {SD} difference between proband and parental report, 1.36 years {9.07 years}, and cigarettes per day and brand smoked kappa = .49 and .56, respectively) but poor agreement for items that may represent more complex or less observable indicators of nicotine dependence, regardless of parental smoking status. Reliability was excellent for probands of either current- or exsmoker parents for smoking status (kappa = .92). As a result of probands' difficulty in reliably answering several items that comprise the Fagerström Tolerance Questionnaire (FTQ) (e.g., number of minutes to parent's first cigarette of the day, whether parent smoked more in the morning than during the rest of the day) and the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) diagnosis (e.g., sleep difficulties and difficulty concentrating during nicotine withdrawal), reliability for an FTQ score ≥7 (kappa = .067) and the DSM-IV nicotine dependence diagnosis (kappa = .28) was poor. Our findings should aid investigators in defining the limits of proband reports of parental smoking behavior and identify opportunities for the development of better approaches for the assessment of familial nicotine dependence.
Although considerable progress has been made towards understanding the role of menstrual cycle phase in smoking, little is known about the possible effects of menstrual phase upon nicotine intake, ...withdrawal symptomatology, and craving in women with psychiatric cofactors. Fourteen women with and without a history of Major Depressive Disorder (MDD) were studied during five biologically-confirmed phases over the course of one menstrual cycle; smoking logs, salivary cotinine, and ratings of craving and withdrawal were collected daily. During a second cycle, subjects remained abstinent for 3 consecutive days during the postmenses and premenstrual phases. Although a significant omnibus
F-test emerged for cigarettes per day across phases during ad libitum smoking, only trends were observed post hoc and supported midcycle rather than premenstrual elevations. There were no significant phase differences for cotinine. Withdrawal symptomatology was markedly elevated during smoking abstinence and in women with a history of depression, but showed no evidence of phase effects. Thus, the hypothesis that depressed individuals would be differentially affected by phase and abstinence was not strongly supported by our results, though overall elevations emphasize the need for special attention to withdrawal severity in this population. Craving was significantly elevated during smoking abstinence and was significantly higher during postmenses, consistent with the midcycle elevation in smoking rate, but showed no group differences. Our findings overall lend little support for the need to control for menstrual phase under conditions of ad libitum smoking. The strong association of self-reported menstrually related dysphoria during abstinence with both craving and withdrawal symptoms, however, is consistent with an exacerbation of smoking abstinence effects in women with severe menstrual symptomatology.
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