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Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence

Baker, Travis E.; Castellanos-Ryan, Natalie; Schumann, Gunter; Cattrell, Anna; Flor, Herta; Nees, Frauke; Banaschewski, Tobias; Bokde, Arun L.W.; Whelan, Rob; Buechel, Christian; Bromberg, Uli; Orfanos, Dimitri Papadopoulos; Gallinat, Jürgen; Garavan, Hugh; Heinz, Andreas; Walter, Henrik; Brühl, Rüdiger; Gowland, Penny A.; Paus, Tomáš; Poustka, Luise; Martinot, Jean-Luc; Lemaitre, Hervé; Artiges, Eric; Martinot, Marie-Laure Paillère; Smolka, Michael N.; Conrod, Patricia J.

Authors

Travis E. Baker

Natalie Castellanos-Ryan

Gunter Schumann

Anna Cattrell

Herta Flor

Frauke Nees

Tobias Banaschewski

Arun L.W. Bokde

Rob Whelan

Christian Buechel

Uli Bromberg

Dimitri Papadopoulos Orfanos

Jürgen Gallinat

Hugh Garavan

Andreas Heinz

Henrik Walter

Rüdiger Brühl

Tomáš Paus

Luise Poustka

Jean-Luc Martinot

Hervé Lemaitre

Eric Artiges

Marie-Laure Paillère Martinot

Michael N. Smolka

Patricia J. Conrod



Abstract

Background: Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both.

Methods: In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum and orbital frontal cortex, and whether this relationship predicted the propensity to engage in early alcohol misuse behaviours at 14 years of age and again at 16 years of age.
Results: The results demonstrated a regional specificity with which the functional polymorphism rs686 of the DRD1 gene and Taq1A of the ANKK1 gene influenced medial and lateral orbital frontal cortex activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial orbital frontal cortex and the ventral striatum interaction.
Conclusions: These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse.

Citation

Baker, T. E., Castellanos-Ryan, N., Schumann, G., Cattrell, A., Flor, H., Nees, F., …Conrod, P. J. (in press). Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence. Psychological Medicine, doi:10.1017/S0033291718001459

Journal Article Type Article
Acceptance Date Apr 16, 2018
Online Publication Date Jun 18, 2018
Deposit Date Apr 18, 2018
Publicly Available Date Dec 19, 2018
Journal Psychological Medicine
Print ISSN 0033-2917
Electronic ISSN 1469-8978
Publisher Cambridge University Press (CUP)
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1017/S0033291718001459
Keywords adolescence; dopamine D1/D2 receptor; ventral striatum; orbital frontal cortex; reward; addiction
Public URL http://eprints.nottingham.ac.uk/id/eprint/51240
Publisher URL https://www.cambridge.org/core/journals/psychological-medicine/article/modulation-of-orbitofrontalstriatal-reward-activity-by-dopaminergic-functional-polymorphisms-contributes-to-a-predisposition-to-alcohol-misuse-in-early-adolescence/616F5E24313D3563B324
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf


MS_Baker_et_al_2018_revision (002).pdf (780 Kb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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