Multi-site exploration of sex differences in brain reactivity to smoking cues: Consensus across sites and methodologies

- We compared brain activity to smoking cues between nicotine dependent men and women.
- This multi-site replication used two new cohorts and multiple imaging modalities.
- Men show higher reactivity to smoking cues in reward-related brain areas than women.
- Brain reactivity during smoking cues correlate with subjective craving in men only.
- Similar results in both cohorts demonstrate rigor and reproducibility of our data.

BackgroundBiological sex influences cigarette smoking behavior. More men than women smoke, but women have a harder time quitting. Sex differences in smoking cue (SC) reactivity may underlie such behavioral differences. However, the influence of sex on brain reactivity to SCs has yielded inconsistent findings suggesting the need for continued study. Here, we investigated the effect of sex on SC reactivity across two sites using different imaging modalities and SC stimulus types.MethodsPseudo-continuous arterial spin-labeled (pCASL) perfusion functional magnetic resonance imaging (fMRI) was used to assess brain responses to SC versus non-SC videos in 40 smokers (23 females) at the University of Pennsylvania. BOLD fMRI was used to assess brain responses to SC versus non-SC still images in 32 smokers (18 females) at McLean Hospital. Brain reactivity to SCs was compared between men and women and was correlated with SC-induced craving.ResultsIn both cohorts, males showed higher SC versus non-SC reactivity compared to females in reward-related brain regions (i.e., ventral striatum/ventral pallidum, ventral medial prefrontal cortex). Brain activation during SC versus non-SC exposure correlated positively with SC-induced subjective craving in males, but not females.ConclusionsThe current work provides much needed replication and validation of sex differences in SC-reactivity. These findings also add to a body of literature showing that men have greater reward-related brain activation to drug cues across drug classes. Such sex differences confirm the need to consider sex not only when evaluating SC-reactivity but when examining nicotine dependence etiology and treatment.