Sex Differences in the Association of Cigarette Craving With Insula Structure

Abstract

Background: Cigarette craving, which can negatively impact smoking cessation, is reportedly stronger in women than in men when they initiate abstinence from smoking. Identifying approaches to counteract craving in people of different sexes may facilitate the development of personalized treatments for Tobacco Use Disorder, which disproportionately affects women. Because cigarette craving is associated with nicotine dependence and structure of the insula, this study addressed whether a person's sex influences these associations.

Methods: The research participants (n = 99, 48 women) reported daily cigarette smoking and provided self-reports of nicotine dependence. After overnight abstinence from smoking, they underwent structural magnetic resonance imaging scanning to determine cortical thickness of the left and right anterior circular insular sulcus, and self-rated their cigarette craving before and after their first cigarette of the day.

Results: Women reported stronger craving than men irrespective of smoking condition (i.e., pre- and post-smoking) (P = .048), and smoking reduced craving irrespective of sex (P < .001). A 3-way interaction of sex, smoking condition, and right anterior circular insular sulcus thickness on craving (P = .033) reflected a negative association of cortical thickness with pre-smoking craving in women only (P = .012). No effects of cortical thickness in the left anterior circular insular sulcus were detected. Nicotine dependence was positively associated with craving (P < .001) across groups and sessions, with no sex differences in this association.

Conclusions: A negative association of right anterior insula thickness with craving in women only suggests that this region may be a relevant therapeutic target for brain-based smoking cessation interventions in women.

Keywords: Craving; insula; nicotine dependence; sex differences; smoking.

Figure 1.

Effects of sex, resumption of smoking, and nicotine dependence on cigarette craving. Nicotine dependence (Heaviness of Smoking Index [HSI]) was measured in men (n = 51) and women (n = 48), and craving was measured after overnight (approximately 12 hours) smoking abstinence, before and after the first cigarette of the day. (A) There were main effects of sex (P = .048) (women reported greater craving than men) and smoking (P < .001) (men and women reported less craving after vs before smoking) on craving. (B) There was also a main effect of HSI on craving (P < .001) (individuals with greater nicotine dependence reported greater craving, irrespective of sex or smoking condition). Means ± SD shown.

Figure 2.

Sex differences in the relationship between insula thickness and cigarette craving. Mean thickness (mm) within the anterior insula, within each hemisphere, was measured in men (n = 44) and women (n = 40), and craving was measured after overnight (approximately 12 hours) smoking abstinence. (A) A rendered “inflated” brain (top left) as well as coronal (top right), transaxial (bottom left), and sagittal (bottom right) brain views, showing the FreeSurfer parcellations for which thickness was determined: the right (green) and left (yellow) anterior circular insular sulcus. (B) There was a 3-way interaction of sex, smoking condition, and right anterior circular insular sulcus thickness on craving (P = .033). Post hoc analyses showed that mean insula thickness was negatively associated with craving in abstinent women only (P = .012).