Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence
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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; Whelan, Rob; Buechel, Christian; Bromberg, Uli; Papadopoulos Orfanos, Dimitri; Gallinat, Juergen; Garavan, Hugh; Heinz, Andreas; Walter, Henrik; Brühl, Rüdiger; Gowland, Penny; Paus, Tomáš; Poustka, Luise; Martinot, Jean-Luc; Lemaitre, Herve; Artiges, Eric; Paillère Martinot, Marie-Laure; Smolka, Michael N; Conrod, Patricia; IMAGEN Consortium.
in: PSYCHOL MED, Jahrgang 49, Nr. 5, 04.2019, S. 801-810.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -