McGeary John E, Esposito-Smythers Christianne, Spirito Anthony, Monti Peter M
Providence Veterans Affairs Medical Center, Providence, Rhode Island, USA.
Pharmacol Biochem Behav. 2007 Feb;86(2):401-6. doi: 10.1016/j.pbb.2006.11.001. Epub 2006 Dec 15.
The VNTR polymorphism in the Dopamine D4 receptor gene (DRD4) has been associated with differential urge for substances across multiple methodologies ranging from neuroimaging to assessment in the natural environment. It is unclear whether the DRD4 gene is a marker for an underlying propensity for greater urge or whether the DRD4 gene differentially moderates the neuroadaptive effects of extended substance use on urge. Examination of the DRD4 in an adolescent sample may provide evidence of a mechanism of this putative relationship.
Data from a subset of 77 participants in a larger assessment study characterized adolescents for substance-related behaviors by DRD4 genotype. The psychiatrically admitted adolescents were genotyped for the variable number of tandem repeats polymorphism in the DRD4 gene (L>or=7 [n=25], S=or<7 [n=52]). Associations of the DRD4 with scores on the SASSI, and ADI were examined as well as selected individual items thought to be most related to the intermediate phenotype of urge.
The DRD4 gene was not associated with any DSM-IV substance misuse diagnostic classification. Individual items related to urge were also nonsignificantly related to DRD4 status. Carriers of the long variant of the DRD4 polymorphism were more likely to have used hard drugs within the previous 6 months and scored higher on the self-medication subscale of the ADI compared to short variant homozygotes.
Preliminary results provide little evidence for the DRD4 VNTR polymorphism to be related to urge-related phenomena in hospitalized adolescents on a psychiatric inpatient unit. The association of the DRD4 gene with hard drug use may support literature linking this gene to impulsivity. Subscale findings may suggest a role of negative affect in previous DRD4 urge findings.
多巴胺D4受体基因（DRD4）中的可变数目串联重复多态性，已通过从神经影像学到自然环境评估等多种方法，与对物质的不同渴望程度相关联。目前尚不清楚DRD4基因是潜在更强渴望倾向的标志物，还是DRD4基因以不同方式调节长期物质使用对渴望的神经适应性影响。在青少年样本中对DRD4进行研究，可能会为这种假定关系的机制提供证据。
在一项更大规模评估研究中，选取77名参与者的子集数据，根据DRD4基因型对青少年的物质相关行为进行特征分析。对因精神疾病入院的青少年进行DRD4基因中串联重复多态性可变数目的基因分型（L≥7 [n = 25]，S≤7 [n = 52]）。研究了DRD4与SASSI和ADI评分之间的关联，以及被认为与渴望中间表型最相关的选定单项。
DRD4基因与任何DSM-IV物质滥用诊断分类均无关联。与渴望相关的单项与DRD4状态也无显著关联。与短变体纯合子相比，DRD4多态性长变体携带者在过去6个月内更有可能使用过硬性毒品，并且在ADI的自我用药子量表上得分更高。
初步结果几乎没有证据表明DRD4 VNTR多态性与精神科住院青少年的渴望相关现象有关。DRD4基因与硬性毒品使用之间的关联可能支持将该基因与冲动性联系起来的文献。子量表研究结果可能表明消极情绪在先前DRD4渴望研究结果中发挥了作用。
