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Trait novelty seeking has been consistently implicated in substance use, yet the origins and mechanisms of novelty seeking in substance use proneness are unclear. We aimed to characterize novelty seeking as a phenotypic marker of substance use proneness in adolescence, a critical period for drug use experimentation. To this end, we parsed novelty seeking’s two constituent subdimensions – exploratory excitability (drive for novel experience) and impulsiveness (careless decision-making) – and explored the individual relations of these dimensions to: (1) the use of a variety of licit and illicit substances, (2) family history of substance use, and (3) subjective drug effects. Five hundred eighty five adolescents (mean age = 14.5 years) completed surveys of key variables. Results indicated that, when accounting for the covariation among exploratory excitability and impulsiveness, impulsiveness emerged as the more salient correlate of substance use and was independently associated with initiation of nearly all drug classes. Mediation analyses of the mechanisms of novelty seeking-related risk illustrated that impulsiveness mediated the association of family history of substance use with both initiation and past 30-day frequency of use. Both impulsiveness and exploratory excitability were associated with increased positive and negative subjective drug effects, and the analyses supported a significant indirect pathway from impulsiveness to a more frequent use via positive subjective effects. Although limited by a cross-sectional design, these findings suggest that impulsiveness-like aspects of the novelty seeking construct may represent a useful phenotypic marker for early substance use proneness that potentially (1) increases initiation risk, (2) has familial origins, and (3) promotes more frequent use by altering subjective drug response.
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