Blum Kenneth, Oscar-Berman Marlene, Demetrovics Zsolt, Barh Debmalya, Gold Mark S
Department of Psychiatry & McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA,
Mol Neurobiol. 2014 Dec;50(3):765-96. doi: 10.1007/s12035-014-8726-5. Epub 2014 May 31.
We have published extensively on the neurogenetics of brain reward systems with reference to the genes related to dopaminergic function in particular. In 1996, we coined "Reward Deficiency Syndrome" (RDS), to portray behaviors found to have gene-based association with hypodopaminergic function. RDS as a useful concept has been embraced in many subsequent studies, to increase our understanding of Substance Use Disorder (SUD), addictions, and other obsessive, compulsive, and impulsive behaviors. Interestingly, albeit others, in one published study, we were able to describe lifetime RDS behaviors in a recovering addict (17 years sober) blindly by assessing resultant Genetic Addiction Risk Score (GARS™) data only. We hypothesize that genetic testing at an early age may be an effective preventive strategy to reduce or eliminate pathological substance and behavioral seeking activity. Here, we consider a select number of genes, their polymorphisms, and associated risks for RDS whereby, utilizing GWAS, there is evidence for convergence to reward candidate genes. The evidence presented serves as a plausible brain-print providing relevant genetic information that will reinforce targeted therapies, to improve recovery and prevent relapse on an individualized basis. The primary driver of RDS is a hypodopaminergic trait (genes) as well as epigenetic states (methylation and deacetylation on chromatin structure). We now have entered a new era in addiction medicine that embraces the neuroscience of addiction and RDS as a pathological condition in brain reward circuitry that calls for appropriate evidence-based therapy and early genetic diagnosis and that requires further intensive investigation.
我们已广泛发表关于大脑奖赏系统神经遗传学的研究，尤其涉及与多巴胺能功能相关的基因。1996年，我们创造了“奖赏缺乏综合征”（RDS）一词，用以描述那些被发现与多巴胺能功能减退存在基因关联的行为。作为一个有用的概念，RDS在许多后续研究中得到应用，以增进我们对物质使用障碍（SUD）、成瘾以及其他强迫性、冲动性和成瘾行为的理解。有趣的是，尽管还有其他研究，但在一项已发表的研究中，我们仅通过评估由此产生的遗传成瘾风险评分（GARS™）数据，就能盲目地描述一名康复成瘾者（已戒酒17年）一生的RDS行为。我们假设，早期进行基因检测可能是一种有效的预防策略，可减少或消除病理性物质和行为寻求活动。在此，我们考虑一些特定的基因、它们的多态性以及与RDS相关的风险，通过全基因组关联研究（GWAS），有证据表明这些基因汇聚于奖赏候选基因。所呈现的证据作为一种似是而非的脑图谱，提供了相关的遗传信息，这将加强靶向治疗，并在个体基础上改善康复效果和预防复发。RDS的主要驱动因素是多巴胺能功能减退特征（基因）以及表观遗传状态（染色质结构上的甲基化和去乙酰化）。我们现在已进入成瘾医学的新时代，该时代将成瘾神经科学和RDS视为大脑奖赏回路中的一种病理状况，这需要适当的循证治疗、早期基因诊断，并且需要进一步深入研究。
