Department of Psychiatry,Universite de Montreal, CHU Ste Justine Hospital,Montreal,Canada.
Institute of Psychiatry, King's College London,London,UK.
Psychol Med. 2019 Apr;49(5):801-810. doi: 10.1017/S0033291718001459. Epub 2018 Jun 18.
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.
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.
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.
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.
异常的奖励回路功能被认为是成瘾的核心特征。然而，这些异常是源于慢性药物使用、遗传倾向还是两者兼而有之，目前还知之甚少。
在本研究中，我们通过结构方程模型来研究这个问题，该模型应用于一个青少年儿童的大样本，以考察 D1 和 D2 受体类型的几种多巴胺能多态性对腹侧纹状体（VS）和眶额皮层（OFC）的奖励功能的影响，以及这种关系是否预测了 14 岁和 16 岁时早期饮酒行为的倾向。
结果表明，D1 多巴胺受体（DRD1）基因的功能性多态性 rs686 和 ANKK1 基因的 Taq1A 分别影响内侧和外侧 OFC 在奖励预期期间的激活，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 与早期酒精滥用的发生通过内侧 OFC×VS 相互作用存在显著的间接关系。
这些发现强调了 D1 和 D2 在调节中边缘皮质回路中的奖励相关激活中的作用，以及在易感性早期酒精滥用中的作用。
