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.

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, https://doi.org/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
• 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: https://nottingham-repository.worktribe.com/output/939352
• 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