Sex Differences in Resting State Brain Function of Cigarette Smokers and Links to Nicotine Dependence

Abstract

Sex – a marker of biological and social individual differences – matters for drug use, particularly for cigarette smoking, which is the leading cause of preventable death in the United States. More men than women smoke, but women are less likely than men to quit. Resting state brain function, or intrinsic brain activity that occurs in the absence of a goal-directed task, is important for understanding cigarette smoking, as it has been shown to differentiate between smokers and non-smokers. But, it is unclear whether and how sex influences the link between resting state brain function and smoking behavior. In this study, we demonstrate that sex is indeed associated with resting state connectivity in cigarette smokers, and that sex moderates the link between resting state connectivity and self-reported nicotine dependence. Using functional magnetic resonance imaging and behavioral data from 50 adult daily smokers (23 women), we found that women had greater connectivity than men within the default mode network, and that increased connectivity within the reward network was related to increased nicotine tolerance in women but to decreased nicotine tolerance in men. Findings highlight the importance of sex-related individual differences reflected in resting state connectivity for understanding the etiology and treatment of substance use problems.