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Evidence for the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS). DRD2基因作为奖励缺乏综合征(RDS)决定因素的证据。
Pub Date : 2023-06-29
Kenneth Blum, Abdala Bowirrat, Igor Elman, David Baron, Panayotis K Thanos, Mark S Gold, Colin Hanna, Milan T Makale, Keerthy Sunder, Nicole Jafari, Foojan Zeine, Kevin T Murphy, Miles Makale, Rajendra D Badgaiyan

Since 1990, published addiction psychiatry articles have exceeded 11,495. Several from Blum et al. showed the clinical relevance of the Genetic Addiction Risk Severity (GARS) test in identifying risk for reward deficiency behaviors in cohorts from polysubstance and pain clinics, post-surgical bariatrics, and DWI offenders facing prison time. Since Blum et al first published in JAMA (1990) concerning the association of the DRD2 gene polymorphism and severe alcoholism, confirmation has been mixed and controversial. More recently, however, a meta-analysis of 62 studies showed a significant association between DRD2 rs 1800497 and Alcohol Use Disorder (AUD). Other studies from Yale University showed that a haplotype block of the DRD2 gene A1 allele was associated with AUD and heroin dependence. GWAS studies of depression and suicide in 1.2 million veterans confirmed the first psychiatric candidate gene study finding from Blum et al. 1990; a significant association between the minor DRD2 allele, Taq A1 (rs 1800497 C>T) and severe alcoholism. Additionally, the DRD2 rs1800497 is associated with suicide behaviors robustly at P=1.77 × 10-7. Furthermore, DNA polymorphic alleles underlying SUD with multiple substances were mapped via chromatin refolding, revealed that the DRD2 gene and associated polymorphism(s) was the top gene signal (DRD2, P=7.9 × 10-12). Additionally, based on these investigations, we conclude that GWAS should end the controversy about the DRD2 gene being at least one determinant of Reward Deficiency Syndrome (RDS) first reported in the Royal Society of Medicine journaling 1996.

自1990年以来,发表的成瘾精神病学文章已超过11495篇。Blum等人的几项研究显示了遗传成瘾风险严重程度(GARS)测试在识别来自多物质和疼痛诊所、术后减肥患者和面临监禁的酒后驾车罪犯的奖励缺乏行为风险方面的临床相关性。自Blum等人于1990年首次在JAMA上发表关于DRD2基因多态性与严重酒精中毒的关联的文章以来,对其的证实一直存在分歧和争议。然而,最近一项对62项研究的荟萃分析显示,DRD2 rs 1800497与酒精使用障碍(AUD)之间存在显著关联。耶鲁大学的其他研究表明,DRD2基因A1等位基因的单倍型阻滞与AUD和海洛因依赖有关。GWAS对120万退伍军人的抑郁和自杀的研究证实了Blum等人1990年的第一个精神病学候选基因研究发现;次要DRD2等位基因taqa1 (rs 1800497 C>T)与严重酒精中毒之间存在显著关联。此外,DRD2 rs1800497与自杀行为显著相关(P=1.77 × 10-7)。此外,通过染色质重折叠定位了与SUD相关的多物质DNA多态性等位基因,发现DRD2基因及其相关多态性(s)是顶级基因信号(DRD2, P=7.9 × 10-12)。此外,基于这些研究,我们得出结论,GWAS应该结束关于DRD2基因是奖励缺乏综合征(RDS)的至少一个决定因素的争议,该争议首次在1996年英国皇家医学学会杂志上报道。
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引用次数: 0
Beyond Mor: Can Induction of Dopamine Homeostasis Along with Electrotherapy Attenuate the Opioid Crisis? 超越摩尔:在电疗的同时诱导多巴胺平衡能否缓解阿片类药物危机?
Pub Date : 2023-03-02
Kenneth Blum, Abdalla Bowirrat, Eric R Braverman, Catherine Dennen, Foojan Zeine, Nicole Jafari, Keerthy Sunder, Panayotis K Thanos, David Baron, Debmayla Barh, Ashim Gupta, Debasis Bagchi, Mark S Gold, Rajendra D Badgaiyan

One important area for consideration especially in terms of combating the ongoing never ending opioid crisis, relates to novel newer assessments for all addictive behaviors both substance and non-substance behaviors (RDS). It is very important to identify early in one's life the possibility of, because of known DNA antecedents, the presence of pre-addiction. The development of the Genetic Addiction Risk Severity (GARS) test, Blum's group believes that this type of testing should be the "standard of care" following additional studies. Understandably that while polymorphisms in the Mu-Opioid receptor (MOR) is of real concern in terms of setting people up for predisposition to opioid dependence, the genetic and epigenetic status of dopaminergic function must be considered as well. While this sounds bold (which it is) the results should be protected by the G.I. N. A. law enacted in the USA in 2011. One avenue of further investigation, instead of providing powerful opioids for opioid dependence, is to seek out non-addictive alternatives. Accordingly, other non-addictive modalities including genetic guided KB220 (amino-acid-enkephalinase-N-acetylcysteine-NAD), non-invasive rTMS for psychiatry and pain, epigenetic remodeling, gene edits, non-invasive H-wave for pain management and enhanced functionality, brain spotting, cognitive behavioral therapy awarenesss integration therapy, NUCALM, trauma therapy, awareness tools, genograms, exercise, sports, fitness programs (one hour per day), light therapy and even laughing therapy as well as any other known modalities that can induce reward symmetry. While the short term use of opioids for opioid dependence to reduce harm is certainly acceptable, clinicians should consider a better long-term plan.

需要考虑的一个重要领域,尤其是在应对持续不绝的阿片类药物危机方面,与针对所有成瘾行为(包括药物和非药物行为)的新型评估有关。由于已知的 DNA 前因,在生命早期识别是否存在成瘾前兆非常重要。布卢姆的研究小组开发了遗传成瘾风险严重程度(GARS)测试,并认为在进行更多研究后,这种测试应成为 "护理标准"。可以理解的是,虽然缪-阿片受体(MOR)的多态性是人们对阿片依赖易感性的真正关注点,但多巴胺能功能的遗传和表观遗传状况也必须考虑在内。虽然这听起来很大胆(确实如此),但研究结果应受到美国 2011 年颁布的 G.I. N. A. 法的保护。进一步研究的一个途径是寻找非成瘾性替代品,而不是提供强效阿片类药物来治疗阿片类药物依赖。因此,其他非成瘾性方式包括基因引导的 KB220(氨基酸-脑啡肽酶-N-乙酰半胱氨酸-NAD)、用于精神病和疼痛的无创经颅磁刺激、表观遗传重塑、基因编辑、用于疼痛管理和增强功能的无创 H 波、脑斑、认知行为疗法、意识整合疗法、NUCALM、创伤疗法、意识工具、基因图、运动、体育、健身计划(每天一小时)、光疗、甚至笑疗以及任何其他可诱导奖赏对称的已知方式。短期使用阿片类药物治疗阿片类药物依赖以减少伤害当然是可以接受的,但临床医生应考虑更好的长期计划。
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引用次数: 0
Overlapping Risky Decision-Making and Olfactory Processing Ability in HIV-Infected Individuals. 艾滋病病毒感染者的风险决策和嗅觉处理能力相互重叠。
Pub Date : 2017-09-01 Epub Date: 2017-08-15 DOI: 10.4172/2471-2701.1000160
Christopher Jackson, Narayan Rai, Charlee K McLean, Maria Mananita S Hipolito, Flora Terrell Hamilton, Suad Kapetanovic, Evaristus A Nwulia

Objective: Given neuroimaging evidences of overlap in the circuitries for decision-making and olfactory processing, we examined the hypothesis that impairment in psychophysical tasks of olfaction would independently predict poor performances on Iowa Gambling Task (IGT), a laboratory task that closely mimics real-life decision-making, in a US cohort of HIV-infected (HIV+) individuals.

Method: IGT and psychophysical tasks of olfaction were administered to a Washington DC-based cohort of largely African American HIV+ subjects (N=100), and to a small number of demographically-matched non-HIV healthy controls (N=43) from a different study. Constructs of olfactory ability and decision-making were examined through confirmatory factor analysis (CFA). Structural equation models (SEMs) were used to evaluate the validity of the path relationship between these two constructs.

Result: The 100 HIV+ participants (56% female; 96% African Americans; median age = 48 years) had median CD4 count of 576 cells/μl and median HIV RNA viral load <48 copies per milliliter. Majority of HIV+ participants performed randomly throughout the course of IGT tasks, and failed to demonstrate a learning curve. Confirmatory factor analysis provided support for a unidimensional factor underlying poor performances on IGT. Nomological validity for correlations between olfactory ability and IGT performance was confirmed through SEM. Finally, factor scores of olfactory ability and IGT performance strongly predicted 6 months history of drug use, while olfaction additionally predicted hallucinogen use.

Conclusion: This study suggests that combination of simple, office-based tasks of olfaction and decision-making may identify those HIV+ individuals who are more prone to risky decision-making. This finding may have significant clinical, public health value if joint impairments in olfaction and IGT task correlates with more decreased activity in brain regions relevant to decision-making.

研究目的鉴于有神经影像学证据表明决策和嗅觉处理回路存在重叠,我们研究了这样一个假设:在美国艾滋病病毒感染者(HIV+)队列中,嗅觉心理物理任务的损伤将独立预测爱荷华赌博任务(IGT)的不良表现,这是一项与现实生活中的决策密切相关的实验室任务:方法:对华盛顿特区的一组主要为非裔美国人的 HIV 感染者(100 人)和来自另一项研究的少量人口统计学匹配的非 HIV 健康对照者(43 人)进行了 IGT 和嗅觉心理物理任务测试。通过确证因子分析(CFA)对嗅觉能力和决策的结构进行了研究。结构方程模型(SEM)用于评估这两个构念之间路径关系的有效性:结果:100 名 HIV 感染者(56% 为女性;96% 为非裔美国人;年龄中位数为 48 岁)的 CD4 细胞计数中位数为 576 cells/μl,HIV RNA 病毒载量中位数为 576 cells/μl:这项研究表明,将简单的办公室嗅觉和决策任务相结合,可以识别出那些更容易做出危险决策的 HIV 感染者。如果嗅觉和 IGT 任务的共同损伤与决策相关脑区活动的减少相关联,那么这一发现可能具有重要的临床和公共卫生价值。
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引用次数: 0
Apo E4 Alleles and Impaired Olfaction as Predictors of Alzheimer's Disease. 载脂蛋白 E4 等位基因和嗅觉受损是阿尔茨海默病的预测因素。
Pub Date : 2017-01-01 Epub Date: 2017-10-19 DOI: 10.4172/2471-2701.1000169
Magdalena M Misiak, MariaMananita S Hipolito, Habtom W Ressom, Thomas O Obisesan, Kebreten F Manaye, Evaristus A Nwulia

Alzheimer's disease (AD) is the most common form of dementia that affects more than 5 million Americans. It is the only disease among the 10 causes of death that cannot be slowed or cured, thus raising the need for identification of early preclinical markers that could be the focus of preventative efforts. Although evidence is escalating that abnormalities in olfactory structure and function precede AD development and early cognitive impairments by one or more decades, the importance of olfaction is largely overlooked in AD, and such testing is not routinely performed in neurology clinics. Nevertheless, research using the olfactory model, has begun to advance our understanding of the preclinical pathophysiology of AD. Notably, an interesting series of studies is beginning to illuminate the relationship between Apolipoprotein E (ApoE) ε4 polymorphism and olfactory dysfunction and late-onset Alzheimer's disease. In this article, we reviewed present research on the significance of ApoE and olfaction to AD, summarized current studies on the associations and mechanisms of ApoE and olfactory dysfunction, and highlighted important gaps for future work to further advance the translational application of the olfactory paradigm to early, preclinical diagnosis and treatment of AD.

阿尔茨海默病(AD)是最常见的痴呆症,影响着 500 多万美国人。它是十大死因中唯一无法减缓或治愈的疾病,因此需要识别早期临床前标志物,作为预防工作的重点。尽管越来越多的证据表明,嗅觉结构和功能的异常早于注意力缺失症的发生和早期认知障碍达数十年之久,但嗅觉在注意力缺失症中的重要性在很大程度上却被忽视了,神经病学诊所也没有常规进行此类测试。然而,利用嗅觉模型进行的研究已开始促进我们对艾滋病临床前病理生理学的了解。值得注意的是,一系列有趣的研究开始揭示载脂蛋白 E(载脂蛋白E)ε4 多态性与嗅觉功能障碍和晚发性阿尔茨海默病之间的关系。在这篇文章中,我们回顾了目前有关载脂蛋白 E 和嗅觉对老年痴呆症的意义的研究,总结了目前有关载脂蛋白 E 和嗅觉功能障碍的关联和机制的研究,并强调了未来工作的重要差距,以进一步推动嗅觉范例在早期、临床前诊断和治疗老年痴呆症方面的转化应用。
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Clinical and experimental psychology
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