Smokers show increased fear responses towards safety signals during fear generalization, independent from acute smoking

Smoking is highly prevalent among patients with anxiety disorders. Previous studies suggest that smokers show altered fear learning as compared to non-smokers. To test the effect of acute smoking on fear learning and generalization, we conducted a fear learning experiment online. 202 healthy subjects learned to differentiate a danger and a safe cue on day 1 and were tested for generalization of threat responses 24 h later. To see if the timing of smoking impacts fear learning, we formed three smoker groups with manipulations of acute smoking and withdrawal at different time-points (each group: n = 46) and one non-smoker control group (n = 64). Smoking manipulations contained a 6 h withdrawal after fear learning, smoking directly before or after fear learning. We found no group differences between smoker manipulation groups for fear learning or generalization. However, we found differences in fear generalization between smokers and non-smokers. Smokers showed increased fear ratings towards the stimulus that has been learned as safe and higher US expectancy to stimuli similar to the safe stimulus, when compared to non-smokers. Smoking might constitute a risk factor for impaired discrimination between danger and safety and smoking restrictions could be an effective way to reduce the risks of development or maintenance of anxiety disorders.