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Low smoking-exposure, the adolescent brain, and the modulating role of CHRNA5 polymorphisms

Chaarani, Bader; Kan, Kees-Jan; Mackey, Scott; Spechler, Philip A.; Potter, Alexandra; Orr, Catherine; D'Alberto, Nicholas; Hudson, Kelsey E.; Banaschewski, Tobias; Bokde, Arun L.W.; Bromberg, Uli; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J.; Desrivières, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Martinot, Jean-Luc; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Paus, Tomáš; Poustka, Luise; Smolka, Michael N.; Walter, Henrik; Whelan, Robert; Higgins, Stephen T.; Schumann, Gunter; Althoff, Robert R.; Stein, Elliot A.; Garavan, Hugh

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Bader Chaarani

Kees-Jan Kan

Scott Mackey

Philip A. Spechler

Alexandra Potter

Catherine Orr

Nicholas D'Alberto

Kelsey E. Hudson

Tobias Banaschewski

Arun L.W. Bokde

Uli Bromberg

Christian Büchel

Anna Cattrell

Patricia J. Conrod

Sylvane Desrivières

Herta Flor

Vincent Frouin

Jürgen Gallinat

Andreas Heinz

Bernd Ittermann

Jean-Luc Martinot

Frauke Nees

Dimitri Papadopoulos-Orfanos

Tomáš Paus

Luise Poustka

Michael N. Smolka

Henrik Walter

Robert Whelan

Stephen T. Higgins

Gunter Schumann

Robert R. Althoff

Elliot A. Stein

Hugh Garavan


© 2019 Background: Studying the neural consequences of tobacco smoking during adolescence, including those associated with early light use, may help expose the mechanisms that underlie the transition from initial use to nicotine dependence in adulthood. However, only a few studies in adolescents exist, and they include small samples. In addition, the neural mechanism, if one exists, that links nicotinic receptor genes to smoking behavior in adolescents is still unknown. Methods: Structural and diffusion tensor magnetic resonance imaging data were acquired from a large sample of 14-year-old adolescents who completed an extensive battery of neuropsychological, clinical, personality, and drug-use assessments. Additional assessments were conducted at 16 years of age. Results: Exposure to smoking in adolescents, even at low doses, is linked to volume changes in the ventromedial prefrontal cortex and to altered neuronal connectivity in the corpus callosum. The longitudinal analyses strongly suggest that these effects are not preexisting conditions in those who progress to smoking. There was a genetic contribution wherein the volume reduction effects were magnified in smokers who were carriers of the high-risk genotype of the alpha 5 nicotinic receptor subunit gene, rs16969968. Conclusions: These findings give insight into a mechanism involving genes, brain structure, and connectivity underlying why some adolescents find nicotine especially addictive.


Chaarani, B., Kan, K., Mackey, S., Spechler, P. A., Potter, A., Orr, C., …Garavan, H. (2019). Low smoking-exposure, the adolescent brain, and the modulating role of CHRNA5 polymorphisms. Biological Psychiatry, 4(7), 672-679.

Journal Article Type Article
Acceptance Date Feb 19, 2019
Online Publication Date Mar 15, 2019
Publication Date 2019-07
Deposit Date Mar 11, 2019
Publicly Available Date Mar 16, 2020
Journal Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Print ISSN 0006-3223
Electronic ISSN 2451-9030
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 4
Issue 7
Pages 672-679
Keywords Neuroimaging; Low smoking exposure; Genetics; Grey matter volume; fMRI; adolescents
Public URL
Publisher URL


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