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

TY - JOUR

T1 - Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence

AU - Baker, Travis E

AU - Castellanos-Ryan, Natalie

AU - Schumann, Gunter

AU - Cattrell, Anna

AU - Flor, Herta

AU - Nees, Frauke

AU - Banaschewski, Tobias

AU - Bokde, Arun

AU - Whelan, Rob

AU - Buechel, Christian

AU - Bromberg, Uli

AU - Papadopoulos Orfanos, Dimitri

AU - Gallinat, Juergen

AU - Garavan, Hugh

AU - Heinz, Andreas

AU - Walter, Henrik

AU - Brühl, Rüdiger

AU - Gowland, Penny

AU - Paus, Tomáš

AU - Poustka, Luise

AU - Martinot, Jean-Luc

AU - Lemaitre, Herve

AU - Artiges, Eric

AU - Paillère Martinot, Marie-Laure

AU - Smolka, Michael N

AU - Conrod, Patricia

AU - IMAGEN Consortium

PY - 2019/4

Y1 - 2019/4

N2 - 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 (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors 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 D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC 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 OFC × VS 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.

AB - 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 (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors 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 D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC 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 OFC × VS 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.

KW - Journal Article

U2 - 10.1017/S0033291718001459

DO - 10.1017/S0033291718001459

M3 - SCORING: Journal article

C2 - 29909784

VL - 49

SP - 801

EP - 810

JO - PSYCHOL MED

JF - PSYCHOL MED

SN - 0033-2917

IS - 5

ER -