Blum Kenneth, Modestino Edward J, Gondré-Lewis Marjorie C, Neary Jennifer, Siwicki David, Hauser Mary, Barh Debmalya, Steinberg Bruce, Badgaiyan Rajendra D
Department of Psychiatry, University of Florida & McKnight Brain Institute, College of Florida, Gainesville, FL, USA.
Department of Psychiatry, Human Integrated Services Unit University of Vermont Center for Clinical & Translational Science, College of Medicine, Burlington, VT, USA.
Precis Med (Bangalore). 2017;2(1):17-22. Epub 2017 Nov 18.
It is a reality that globally opioid deaths have soared for men and women of all social, economic status and age from heroin and fentanyl overdoses. Specifically, in the United States, deaths from narcotic overdoses have reached alarming metrics since 2010. In fact, the Fentanyl rise is driven by drug dealers who sell it as heroin or who use it to lace cocaine or to make illegal counterfeit prescription opioids. The President's Commission on the crisis has linked the death toll as equivalent to "September 11th every three weeks." In fact, The U.S. Centre for Disease Control (CDC) released data showing that opioid-related overdoses were up 15% in the first three quarters of 2016 compared to 2015. Various governmental organizations including NIDA, are actively seeking solutions. However, we argue that unless the scientific community embraces genetic addiction risk coupled with potential precision or personalized medicine to induce "dopamine homeostasis" it will fail. We now have evidence that a ten-gene and eleven single nucleotide polymorphism (SNP) panel predicts Addiction Severity Index (ASI) for both alcohol and drugs of abuse (e.g., Opioids). In a large multi-addiction centre study involving seven diverse treatment programs, the genetic addiction risk score (GARS) was shown to have a predictive relationship with ASI-MV derived alcohol (≥ seven alleles), and other drugs (≥ 4 alleles) severity risk scores. In a number of neuroimaging studies, we also display that in both animal (bench) and abstinent Chinese severe heroin-dependent patients (bedside), BOLD dopamine activation across the brain reward circuitry revealed increases in resting state functional connectivity as well volume connectivity. It is also known that published nutrigenomic (coupling gene polymorphisms with altered KB220z) studies reveal improved clinical outcomes related to obesity.
一个现实情况是，全球范围内，所有社会、经济地位和年龄的男性和女性因海洛因和芬太尼过量服用导致的阿片类药物死亡人数飙升。具体而言，在美国，自2010年以来，麻醉品过量服用导致的死亡人数已达到惊人的程度。事实上，芬太尼的增加是由毒贩推动的，他们将其当作海洛因出售，或者用它来掺杂可卡因，或者制造非法的假冒处方阿片类药物。总统危机委员会将死亡人数与“每三周发生一次9·11事件”相提并论。事实上，美国疾病控制中心（CDC）发布的数据显示，与2015年相比，2016年前三季度与阿片类药物相关的过量服用人数增加了15%。包括美国国家药物滥用研究所（NIDA）在内的各种政府组织都在积极寻求解决方案。然而，我们认为，除非科学界接受基因成瘾风险，并结合潜在的精准或个性化医学来诱导“多巴胺内稳态”，否则将会失败。我们现在有证据表明，一个包含十个基因和十一个单核苷酸多态性（SNP）的检测 panel 可以预测酒精和滥用药物（如阿片类药物）的成瘾严重程度指数（ASI）。在一项涉及七个不同治疗项目的大型多成瘾中心研究中，基因成瘾风险评分（GARS）与ASI-MV衍生的酒精（≥七个等位基因）和其他药物（≥四个等位基因）严重程度风险评分具有预测关系。在一些神经影像学研究中，我们还表明，在动物（实验台）和禁欲的中国重度海洛因依赖患者（床边）中，大脑奖赏回路中的BOLD多巴胺激活显示静息态功能连接以及体积连接均增加。众所周知，已发表的营养基因组学（将基因多态性与改变的KB220z相结合）研究表明，与肥胖相关的临床结果有所改善。
