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Baker, Travis E. and Castellanos-Ryan, Natalie and Schumann, Gunter and Cattrell, Anna and Flor, Herta and Nees, Frauke and Banaschewski, Tobias and Bokde, Arun L.W. and Whelan, Rob and Buechel, Christian and Bromberg, Uli and Orfanos, Dimitri Papadopoulos and Gallinat, Jürgen and Garavan, Hugh and Heinz, Andreas and Walter, Henrik and Brühl, Rüdiger and Gowland, Penny A. and Paus, Tomáš and Poustka, Luise and Martinot, Jean-Luc and Lemaitre, Hervé and Artiges, Eric and Martinot, Marie-Laure Paillère and Smolka, Michael N. and Conrod, Patricia J. (2018) Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence. Psychological Medicine . ISSN 1469-8978

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.

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