Blum K, Bowirrat A, Baron D, Lott L, Ponce J V, Brewer R, Siwicki D, Boyett B, Gondre-Lewis M C, Smith D E, Panayotis K Thanos, Badgaiyan S, Hauser M, Fried L, A Roy, Downs B W, Badgaiyan R D
Western University Health Sciences Graduate School of Biomedical Sciences, Pomona, CA, USA.
Department of Precision Behavioral Management, Geneus Health, San Antonio, TX, USA.
J Syst Integr Neurosci. 2020 Aug;6(2). doi: 10.15761/JSIN.1000221. Epub 2019 Dec 19.
Research into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) includes all drug and non-drug addictive, obsessive and compulsive behaviors. We are proposing herein that a new model for the prevention and treatment of Substance Use Disorder (SUD) a subset of RDS behaviors, based on objective biologic evidence, should be given serious consideration in the face of a drug epidemic. The development of the Genetic Addiction Risk Score (GARS) followed seminal research in 1990, whereby, Blum's group identified the first genetic association with severe alcoholism published in JAMA. While it is true that no one to date has provided adequate RDS free controls there have been many studies using case -controls whereby SUD has been eliminated. We argue that this deficiency needs to be addressed in the field and if adopted appropriately many spurious results would be eliminated reducing confusion regarding the role of genetics in addiction. However, an estimation, based on these previous literature results provided herein, while not representative of all association studies known to date, this sampling of case- control studies displays significant associations between alcohol and drug risk. In fact, we present a total of cases and controls derived from the current literature. We strongly suggest that while we may take argument concerning many of these so-called controls (e.g. blood donors) it is quite remarkable that there are a plethora of case -control studies indicating selective association of these risk alleles ( measured in GARS) for the most part indicating a hypodopaminergia. The paper presents the detailed methodology of the GARS. Data collection procedures, instrumentation, and the analytical approach used to obtain GARS and subsequent research objectives are described. Can we combat SUD through early genetic risk screening in the addiction field enabling early intervention by the induction of dopamine homeostasis? It is envisaged that GARS type of screening will provide a novel opportunity to help identify causal pathways and associated mechanisms of genetic factors, psychological characteristics, and addictions awaiting additional scientific evidence including a future meta- analysis of all available data -a work in progress.
对成瘾的神经遗传学基础进行的研究,该研究由奖励缺陷综合征(RDS)确定并描述,涵盖所有药物和非药物成瘾、强迫和强迫行为。我们在此提议,面对药物流行的情况,基于客观生物学证据的一种预防和治疗物质使用障碍(SUD,RDS行为的一个子集)的新模型应得到认真考虑。遗传成瘾风险评分(GARS)的发展遵循了1990年的开创性研究,当时,布卢姆的团队在《美国医学会杂志》上发表了首个与严重酒精中毒的基因关联。虽然迄今为止没有人提供足够的无RDS对照组,但有许多使用病例对照的研究,其中SUD已被排除。我们认为该领域需要解决这一缺陷,如果适当采用,许多虚假结果将被消除,减少关于遗传学在成瘾中作用的困惑。然而,基于本文提供的这些先前文献结果进行的估计,虽然不代表迄今为止所有已知的关联研究,但这种病例对照研究的抽样显示了酒精与药物风险之间的显著关联。事实上,我们展示了从当前文献中得出的总共[X]个病例和[X]个对照。我们强烈建议,虽然我们可能会对许多这些所谓的对照组(例如献血者)存在争议,但有大量病例对照研究表明这些风险等位基因(在GARS中测量)存在选择性关联,在很大程度上表明多巴胺能不足,这是相当值得注意的。本文介绍了GARS的详细方法。描述了用于获得GARS的数据收集程序、仪器以及分析方法和后续研究目标。我们能否通过成瘾领域的早期基因风险筛查来对抗SUD,从而通过诱导多巴胺稳态实现早期干预?预计GARS类型的筛查将提供一个新机会,以帮助识别遗传因素、心理特征和成瘾的因果途径及相关机制,这有待更多科学证据,包括未来对所有可用数据的荟萃分析——一项正在进行的工作。