AIMS: Over the recent decades, smoking among women has become an increasingly pressing public health challenge. Mounting evidence suggests that, compared to men, women's smoking is more strongly influenced by habitual responses to sensorimotor cues. To understand the brain mechanisms underlying the cessation challenges commonly reported by women who smoke, the present study used voxel-based morphometry (VBM) to investigate sex-related volumetric differences in the dorsal striatum, a region implicated in habitual substance use behavior, and their associations with self-reported quit interest among daily smoking adults. METHODS: Structural magnetic resonance imaging (MRI) data were collected from 41 women and 52 men (30.1 ± 7.5 years) who reported smoking an average of 15-40 cigarettes per day for at least past 24 months. Multiple regression analyses were carried out with sex and average gray matter volumes (GMV) of predetermined brain regions of interest (ROIs
bilateral caudate, putamen) and control regions (bilateral nucleus accumbens, thalamus) as predictors of self-reported interest in quitting smoking. FINDINGS: Women displayed greater striatal GMV and lower current quit interest than men. ROI-based analyses revealed an interaction between sex and putamen GMV, wherein putamen GMV was more strongly and negatively linked to quit interest in women than men. CONCLUSIONS: Greater GMV in the putamen could be linked to an attenuated desire to stop smoking among women. This may serve as a neuroanatomical mechanism underlying the higher prevalence of habit-driven smoking behavior observed in women as compared to men.