Association between vmPFC gray matter volume and smoking initiation in adolescents

Smoking of cigarettes among young adolescents is a pressing public health issue. However, the neural mechanisms underlying smoking initiation and sustenance during adolescence, especially the potential causal interactions between altered brain development and smoking behaviour, remain elusive. Here, using large longitudinal adolescence imaging genetic cohorts, we identify associations between left ventromedial prefrontal cortex (vmPFC) gray matter volume (GMV) and subsequent self-reported smoking initiation, and between right vmPFC GMV and the maintenance of smoking behaviour. Rule-breaking behaviour mediates the association between smaller left vmPFCGMV and smoking behaviour based on longitudinal cross-lagged analysis and Mendelian randomisation. In contrast, smoking behaviour associated longitudinal covariation of right vmPFC GMV and sensation seeking (especially hedonic experience) highlights a potential reward-based mechanism for sustaining addictive behaviour. Taken together, our findings reveal vmPFC GMV as a possible biomarker for the early stages of nicotine addiction, with implications for its prevention and treatment.

Automated summary

Smoking initiation and maintenance during adolescence are associated with altered brain development, particularly in the ventromedial prefrontal cortex (vmPFC) gray matter volume (GMV). Rule-breaking behavior mediates the association between smaller left vmPFC GMV and smoking behavior, while a reward-based mechanism involving right vmPFC GMV and sensation seeking is implicated in sustaining addictive behavior. These findings highlight the importance of vmPFC GMV as a possible biomarker for nicotine addiction prevention and treatment.