Association between vmPFC gray matter volume and smoking initiation in adolescents

IMAGEN Consortium, Shitong Xiang, Tianye Jia*, Chao Xie, Wei Cheng, Bader Chaarani, Tobias Banaschewski, Gareth J Barker, Arun L W Bokde, Christian Büchel, Sylvane Desrivières, Herta Flor, Antoine Grigis, Penny A Gowland, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise PoustkaSarah Hohmann, Juliane H Fröhner, Michael N Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Hugh Garavan, Gunter Schumann, Barbara J Sahakian, Trevor W Robbins*, Jianfeng Feng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
3 Downloads (Pure)


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 vmPFC GMV 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.

Original languageEnglish
Article number4684
JournalNature Communications
Issue number1
Publication statusPublished - 15 Aug 2023


  • Humans
  • Adolescent
  • Gray Matter/diagnostic imaging
  • Magnetic Resonance Imaging/methods
  • Prefrontal Cortex/diagnostic imaging
  • Smoking/adverse effects
  • Tobacco Use Disorder
  • Brain


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