is associated with more positive outcomes both subjectively and objectively with respect to feelings of well-being and recovery from ill health (Smith and Spiro, 2002), although the genetic associations have not yet been studied.

Temperament

Of the many methods proposed to assess temperament, perhaps the most widely used is the Temperament and Character Inventory (Cloninger et al., 1998). Four major temperament traits have been identified through factor analysis and investigated in many experiments: harm avoidance, novelty seeking, reward dependence, and persistence (Cloninger et al., 1998). The study of temperament underscores the notion that genetic risk factors for a disease may not be mediated directly by gene function related to the diseased system, but rather by genetic risk factors for psychological traits that change neuroendocrine function and regulate gene expression involved in disease.

Harm avoidance is a measure of behavioral inhibition and fearfulness (Cloninger et al., 1998). Some studies suggest that individuals high in harm avoidance may be more susceptible to tobacco use (Etter et al., 2003). Adrenal axis function may mediate this association since corticotropin releasing factor-like proteins also are associated with prolonged nicotine withdrawal and higher rates of relapse (Bruijnzeel and Gold, 2005).

Novelty seeking is a measure of behavioral activation and excitement seeking that includes subscales measuring exploratory excitability, impulsiveness, extravagance, and a tendency to disorder (Cloninger et al., 1998) that may increase susceptibility to tobacco use by increasing the likelihood that an adolescent will be exposed to environments in which tobacco is more available (Tercyak and Audrain-McGovern, 2003). Novelty seekers also have been shown to be more susceptible to effects of tobacco advertising (Audrain-McGovern et al., 2003b). Animal models indicate that both of these associations also may be mediated by individual differences in adrenal axis function (Piazza et al., 1993; Spina et al., 2005).

Two aspects of temperament (reward dependence and persistence) have been linked with craving during abstinence from gambling and alcohol. Reward dependence is a measure of social attachment (Cloninger et al., 1998) and persistence is a measure of perseverance (Svrakic and Cloninger, 2005). Reward dependence is negatively correlated with craving for gambling, while persistence is negatively associated with craving for alcohol (Tavares et al., 2005). Thus, if nicotine addiction shares mechanisms with other addictions, future research may uncover a role for these other aspects of temperament and their underlying neuroendocrine and pharmacological systems (Svrakic and Cloninger, 2005).

Temperament has also been investigated regarding its association with



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