) Why is relapse far and away the most likely outcome of a cessation attempt? It is difficult to imagine answers to this question that do not implicate tobacco dependence. Dependence is the conceptual nexus integrating the surface features of addiction (e.g., heavy use, severe withdrawal, tendency to relapse, etc.). Greater understanding of the construct linking those phenomena should foster more rapid progress in developing effective treatments. The overarching goal of this research is to develop improved dependence- assessment instruments through theoretical scale construction that focuses on hypothesized mechanisms underlying dependence, rather than on surface manifestations (e.g., cigarettes per day, whether one inhales). Once initial scales are constructed, they will be subjected to diverse validity assessments. Two studies are proposed. In Study I, 460 smokers will be recruited such that they reflect a broad range of dependence. All will participate in a cessation trial with random assignment to 2 or 4 mg nicotine gum or placebo. Three theory-based constructs will serve as chief criteria for the selection of Subscale on the Dependence Questionnaire (DQ): withdrawal severity, pre-cessation smoking heaviness, and relapse. These will be assessed with multiple, sensitive indices. For example, assessments of withdrawal will include measures of both symptom elevation and symptom trajectory. Moreover, over the first five days of cessation, intensive assessment of symptoms will occur via computerized telephone interview. Two additional measures will be gathered because of their strong motivational links to dependence. Genetic markers related to dopaminergic structures and activities will be assessed in all 460 subjects. In addition, a subsample of placebo subjects (N=60) will participate in a behavioral economic assessment, allowing examination of elasticity as a dependence index and providing a further criterion against which to test the DQ. Study 2 (N=400) will employ the same design with two exceptions. First, the study will not involve the elasticity assessment. Second, the active smoking cessation pharmacotherapy will be changed to bupropion so that the stability of the factor structure and predictive validity of the DQ can be determined in a systematic replication. The validity data will address both vital clinical as well as theoretically significant criteria.
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