Smoking patterns vary, and nicotine dependence is complex with many different Crizotinib mechanism phenotypic characteristics. Classically, tolerance and withdrawal symptoms define physical dependence (Victor & Adams, 1953), and inability to stop using a substance despite negative physical, mental, and social consequences defines psychological dependence (Keller, 1972). Most previous research on nicotine dependence has used the Fagerstr?m Test for Nicotine Dependence (FTND) and the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) to index dependence. The FTND scale consists of six questions to measure physical dependence and tolerance processes, and it has been shown to predict cessation (Heatherton, Kozlowski, Frecker, Rickert, & Robinson, 1989).

Two FTND items, time to first cigarette (TTF) and the number of cigarettes smoked per day, have been proposed as simpler measures of nicotine dependence that are especially predictive of successful quitting (Baker et al., 2007; Heatherton et al., 1989). In contrast, DSM-IV nicotine dependence requires a clustering of at least three of seven symptoms intended to index a maladaptive pattern of substance use leading to significant impairment or distress (APA, 1994). Recently, new diagnostic criteria for DSM-V Nicotine Use Disorder have been proposed with changes in threshold and additional symptoms (APA, 2010). The FTND and DSM-IV nicotine dependence criteria capture different aspects of dependence (Hughes et al., 2004). The FTND better predicts smoking cessation, whereas the DSM-IV nicotine dependence diagnosis correlates more strongly with comorbid psychopathology, such as major depressive disorder (Breslau & Johnson, 2000).

Two multifactorial measures have been developed to assess nicotine dependence. The Nicotine Dependence Syndrome Scale (NDSS; Shiffman, Waters, & Hickcox, 2004) comprises scales reflecting Edward��s model of dependence (Edwards, 1986; Edwards & Gross, 1976) in which dependent drug use is compulsive, stereotyped, relatively uninfluenced by external cues, and motivated by strong withdrawal symptoms. The Wisconsin Inventory of Smoking Dependence Motives (WISDM; Piper et al., 2004) assesses multiple distinct motives for dependence that have been supported by extensive research and theory.

Both measures target multiple dimensions of dependence, possess good psychometric properties, and can predict important Dacomitinib dependence symptoms, such as withdrawal and difficulty with cessation (Piper, Bolt, et al., 2008; Piper, McCarthy, & Baker, 2006; Piper, McCarthy, et al., 2008; Shiffman & Sayette, 2005). The use of two multifactorial scales permits the comprehensive coverage of the domain of dependence features and allows us to determine whether the same types of dependence features are associated with genetic variants across both scales (i.e., refine the phenotype). Recent research with the WISDM (Piper, Bolt, et al.