Abstract

Smoking is a significant cause of preventable mortality worldwide. Understanding the neural mechanisms of nicotine addiction and smoking cessation may provide effective targets for developing treatment strategies. In the present study, we explored whether smokers have white matter alterations and whether these alterations are related to cessation outcomes and smoking behaviors. Sixty-six smokers and thirty-seven healthy non-smokers were enrolled. The participants underwent magnetic resonance imaging scans and smoking-related behavioral assessments. After a 12-week treatment with varenicline, 28 smokers succeeded in quitting smoking and 38 failed. Diffusion parameter maps were compared among the non-smokers, future quitters, and relapsers to identify white matter differences. We found that the future relapsers had significantly lower fractional anisotropy (FA) in the orbitofrontal area than non-smokers, and higher FA in the cerebellum than non-smokers and future quitters. The future quitters had significantly lower FA in the postcentral gyrus compared to non-smokers and future relapsers. Compared to non-smokers, pooled smokers had lower FA in bilateral orbitofrontal gyrus and left superior frontal gyrus. In addition, regression analysis showed that the left orbitofrontal FA was correlated with smoking-relevant behaviors. These results suggest that white matter alterations in smokers may contribute to the formation of aberrant brain circuits underlying smoking behaviors and are associated with future smoking cessation outcomes.

Highlights

  • Cigarette smoking is one of the most important causes of preventable mortality worldwide, and has been related to increased risk of respiratory (Dogar et al, 2013) and cardiovascular diseases (Pope et al, 2011)

  • We aimed to demonstrate white matter alterations in smokers, and to investigate whether baseline white matter integrity is associated with smoking behaviors and future cessation outcomes

  • 1http://www.fmrib.ox.ac.uk/fsl were not significantly different in number of years smoked over lifetime (NYS), number of cigarettes smoked per day (CSPD), pack years, or FTND, suggesting that the two groups have similar cigarette consumption and nicotine addiction severity

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Summary

Introduction

Cigarette smoking is one of the most important causes of preventable mortality worldwide, and has been related to increased risk of respiratory (Dogar et al, 2013) and cardiovascular diseases (Pope et al, 2011). Among smokers who are aware of these risks, 3 out of 4 individuals are interested in quitting smoking (Heydari et al, 2014). While many smokers are interested in quitting, the cessation rate remains low, ranging from 12.4% (Hou and Cai, 2014) to about 30% (Brose et al, 2014; Santos et al, 2015). It has been found that smokers have large individual differences in response to current treatments for nicotine dependence (McClernon et al, 2008; Hall et al, 2015). Exploring the neurobiology of nicotine addiction and individual differences in smoking cessation outcomes may help to identify effective targets for developing better treatment strategies.

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