Focus of the center
The University of Wisconsin Transdisciplinary Tobacco Use Research Center (TTURC) has focused on several linked topics: (a) improving our assessment and understanding of nicotine dependence, (b) exploring factors that cause or modulate relapse risk, (c) identifying genetic influences on nicotine dependence and cessation success, and (d) testing smoking cessation interventions and determining their mechanisms of action.
Development of a new multifactorial instrument to assess nicotine dependence.
This developmental research effort produced a new questionnaire that is now being widely used to assess nicotine dependence: the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68), which has good psychometric properties and is appropriate for use with a broad range of smokers (men and women, ethnic minorities; Piper et al., 2004). This work also produced direct evidence that nicotine dependence is indeed multidimensional, revealing which aspects of dependence are most associated with heightened relapse risk, withdrawal severity, and heavy smoking (Piper et al.).
Insight into the nature of nicotine dependence.
Research with the WISDM-68 suggests that four core features of nicotine dependence are both necessary (all groups of significantly dependent smokers have elevations on these subscales) and sufficient (some smokers who are highly dependent have elevated scores only on these subscales) for severe dependence: (a) tolerance, (b) automaticity, (c) loss of control, and (d) craving (Piper, Bolt, et al., 2008). Unlike other dependence motives subscales, scores on these four Primary Dependence Motives subscales tend to show significant increases only after extensive experience with tobacco use and are especially predictive of dependence criteria (e.g., relapse likelihood; Piper et al., 2004). This research suggests that the dependence phenotype can be distilled into a finite set of core features: heavy smoking that is not discriminated on contextual cues; that occurs with little conscious control or mediation; and that is characterized by frequent, strong, and bothersome craving.
Insight into mechanisms via which nicotine dependence leads to relapse back to smoking.
Several studies showed that nicotine withdrawal was highly variable across individuals, that it could persist or increase for several months following cessation (Piasecki, Jorenby, Smith, Fiore, & Baker, 2003a, 2003b, 2003c), and that one outcome of withdrawal was a heightened symptomatic reaction to environmental events (McCarthy, Piasecki, Fiore, & Baker, 2006). This research also showed that craving was especially related to greater likelihood of cessation failure or relapse and that different withdrawal profile dimensions predicted relapse (e.g., the slope of withdrawal, its elevation, and its variability).
The genetics of nicotine dependence.
A collaboration with investigators at the University of Utah examined multiple candidate genes for nicotine dependence (Weiss et al., 2008). This research identified three haplotypes of the CHRNA5-A3-B4 gene cluster that are associated with nicotine dependence severity (indexed by the Fagerström Test for Nicotine Dependence). Further, there is evidence of a gene × environment interaction in which associations between dependence severity and genetic variation are seen in early-onset smokers (daily smoking before age 17) but not in late-onset smokers. This finding has implications for public health measures such as excise taxation that can reduce youth access to and use of tobacco. The research shows that CHRNA5-A3-B4 variants are more highly related to the WISDM-68 Primary Dependence Motives than to other motives, and these variants also predict cessation success.
Characterizing smoking treatment effectiveness.
The effectiveness of multiple interventions for tobacco dependence was explored via several major clinical trials that characterized the effects of counseling and pharmacotherapy (McCarthy et al., 2008; Piper, Federman, et al., 2008; Piper et al., 2004). These showed only modest, transitory effects of counseling, and, although bupropion increased cessation rates, these increases did not persist into long-term follow-up (e.g., 1 year). Moreover, the data suggested that bupropion efficacy was not enhanced by adjuvant nicotine gum. These results underscore the need to develop new and more effective pharmacotherapy and counseling treatment strategies.
How cessation treatments work.
One of the major stumbling blocks to improving cessation interventions and to matching interventions with types of patients is the lack of understanding of how such interventions work. Several papers characterized the significant short-term effects of cessation medications and identified which of these short-term effects are significantly related to long-term outcomes (McCarthy, Bolt, & Baker, 2007; McCarthy et al., 2008; M. E. Piper, E. B. Federman et al., 2008). This research used sophisticated mediational methods, including multilevel and structural equation models to control error and evaluate effects across multiple tests of the compound mediational hypothesis. Results showed that the effects of cessation medication (bupropion) that were most responsible for its long-term benefit were suppression of craving and general withdrawal symptoms and an increase in positive affect. Also, intriguing evidence indicated that the effects of bupropion on quitting motivation and self-efficacy accounted for some of its long-term benefit, suggesting that medication may yield benefit through mechanisms outside of withdrawal suppression.
One raison d’être for transdisciplinary (TD) research is to link observations at different levels of analysis via integrative explanatory mechanisms. The research described here attempts to yield new insights into the nature of nicotine dependence and use them as an integrative mechanism that links data on genetics, relapse vulnerability, and treatment. The research shows that nicotine dependence has core, necessary, and sufficient features consisting of heavy smoking that is not discriminated on contextual cues; that occurs with little conscious control or mediation; and that is characterized by frequent, strong, and bothersome craving. These features are linked to CHRNA5-A3-B4 gene cluster variants, and they predict high self-administration rates, severe withdrawal, and relapse vulnerability. Moreover, pharmacological treatments work, in part, by their ability to suppress elements of the tobacco withdrawal syndrome, a manifestation of this core dependence factor.
Future research efforts will explore further the links among genetics, dependence, and treatment response and will use this information along with treatment research to devise new approaches to the treatment of nicotine dependence.