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

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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. 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

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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.

Item Type: Article
RIS ID: https://nottingham-repository.worktribe.com/output/939352
Keywords: adolescence; dopamine D1/D2 receptor; ventral striatum; orbital frontal cortex; reward; addiction
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Psychology
Identification Number: https://doi.org/10.1017/S0033291718001459
Depositing User: Eprints, Support
Date Deposited: 18 Apr 2018 11:12
Last Modified: 04 May 2020 19:41
URI: https://eprints.nottingham.ac.uk/id/eprint/51240

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