Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence
Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence
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DOI：
10.1017/s0033291718001459
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发表时间：
2019-04-01
影响因子：
6.9
通讯作者：
Conrod, Patricia
中科院分区：
文献类型：
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作者：
Baker, Travis E.;Castellanos-Ryan, Natalie;Conrod, Patricia
背景奖赏回路功能异常被认为是成瘾的核心特征。然而，这些异常是否源于慢性药物使用，遗传易感性或两者兼而有之，在很大程度上仍然是未知的。方法本研究采用结构方程模型，以青少年儿童为研究对象，探讨多巴胺D1和D2受体基因多态性对腹侧纹状体（VS）和眶额皮质（OFC）奖赏功能的影响，以及这种关系是否预测了14岁和16岁时早期酒精滥用行为的倾向。结果D1多巴胺受体（DRD1）基因rs686和ANKK1基因Taq1A多态性分别影响内侧和外侧OFC的激活，并具有区域特异性。重要的是，我们的路径模型揭示了DRD1基因的rs686与酒精滥用的早期发作之间通过中间OFC x VS相互作用的显着间接关系。结论这些发现突出了D1和D2在调节中皮层边缘回路内奖励相关激活中的作用，以及对酒精滥用早期发作的易感性。
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 x 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.