Abstract Introduction Anxiety during acute smoking abstinence is strongly implicated in the maintenance of and lapse/relapse to smoking. Central to anxiety is heightened sensitivity to unpredictable threat—a tendency for anxious apprehension of future, uncertain threat—with work from animal models robustly indicating its contributory role in nicotine seeking behavior during deprivation. However, the handful studies on this question in humans have yielded mixed findings, possibly due to their suboptimal usage of between-subject designs. Consequently, the present study used a within-subject laboratory design to examine whether sensitivity to unpredictable threat mediates the effect of manipulated acute smoking abstinence on smoking lapse behavior. Methods Non-treatment-seeking adults who smoked daily (N=63) attended two counterbalanced experimental sessions under overnight smoking deprivation or smoking as usual. For both sessions, participants completed the No-Predictable-Unpredictable threat task assessing the eyeblink reflex to acoustic startle probes while anticipating electric shocks. Next, participants completed the McKee Experimental Relapse Analogue Task assessing lapse behavior, including the ability to delay smoking for monetary reward and number of cigarettes smoked once initiated. Results As expected, smoking deprivation (vs. smoking as usual) led to shorter time delay to smoking and more cigarettes smoked once initiated. Importantly, sensitivity to unpredictable threat partially mediated abstinence-induced lapse behavior. Deprivation was associated with an enhanced startle potentiation to unpredictable (vs. no) shock—although this effect emerged only in follow-up analyses—which, in turn, predicted increased smoking. Conclusions Sensitivity to unpredictable threat may be an important, but underrecognized, biobehavioral mechanism underlying the smoking-anxiety link. Implications Using a within-subject laboratory design, this study provided preliminary evidence that sensitivity to unpredictable threat may contribute to smoking relapse during acute abstinence. Although these findings await replication in larger samples, they indicate sensitivity to unpredictable threat as a potential biobehavioral target for evaluating anxiety-related processes in smoking cessation interventions.
Li et al. (Wed,) studied this question.