Introduction
premature death, disability, anxiety, threat-of-shock
DISEASE
Tobacco smoking is a leading preventable cause of disease, disability, and premature death in the U.S. and abroad [The transition from tobacco use to nicotine dependence is undoubtedly complex and dynamic, encompassing alterations in multiple motivational and self-regulatory mechanisms [Mechanistic studies in rats and mice motivate the popular hypothesis that withdrawal-related anxiety and stress-induced reinstatement of nicotine use reflect functional alterations in the central extended amygdala (EAc) [Here we used a novel combination of assessments—including questionnaire measures of smoking urges and withdrawal, a well-established certain/uncertain threat-anticipation (‘threat-of-shock’) paradigm, ratings of threat-evoked fear and anxiety, a psychophysiological (skin conductance) measure of threat-evoked arousal, and functional MRI (fMRI)—and a between-subjects randomized trial design to understand the subjective and biological consequences of 24-hour nicotine abstinence in a racially diverse sample of 75 daily tobacco smokers (