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多巴胺能功能障碍:基因与表观遗传检测在新型精神病学中的作用

Dopaminergic dysfunction: Role for genetic & epigenetic testing in the new psychiatry.

作者信息

Blum Kenneth, Ashford J Wesson, Kateb Babak, Sipple Daniel, Braverman Eric, Dennen Catherine A, Baron David, Badgaiyan Rajendra, Elman Igor, Cadet Jean Lud, Thanos Panayotis K, Hanna Colin, Bowirrat Abdalla, Modestino Edward J, Yamamoto Vicky, Gupta Ashim, McLaughlin Thomas, Makale Mlan, Gold Mark S

机构信息

Division of Addiction Research & Education, Center for Exercise, Sports and Mental Health, Western University Health Sciences, Pomona, CA, USA; The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX, USA; Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel.

Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA; War Related Illness & Injury Study Center, VA Palo Alto Health Care System, Palo Alto, CA, USA.

出版信息

J Neurol Sci. 2023 Oct 15;453:120809. doi: 10.1016/j.jns.2023.120809. Epub 2023 Sep 23.

Abstract

Reward Deficiency Syndrome (RDS), particularly linked to addictive disorders, costs billions of dollars globally and has resulted in over one million deaths in the United States (US). Illicit substance use has been steadily rising and in 2021 approximately 21.9% (61.2 million) of individuals living in the US aged 12 or older had used illicit drugs in the past year. However, only 1.5% (4.1 million) of these individuals had received any substance use treatment. This increase in use and failure to adequately treat or provide treatment to these individuals resulted in 106,699 overdose deaths in 2021 and increased in 2022. This article presents an alternative non-pharmaceutical treatment approach tied to gene-guided therapy, the subject of many decades of research. The cornerstone of this paradigm shift is the brain reward circuitry, brain stem physiology, and neurotransmitter deficits due to the effects of genetic and epigenetic insults on the interrelated cascade of neurotransmission and the net release of dopamine at the Ventral Tegmental Area -Nucleus Accumbens (VTA-NAc) reward site. The Genetic Addiction Risk Severity (GARS) test and pro-dopamine regulator nutraceutical KB220 were combined to induce "dopamine homeostasis" across the brain reward circuitry. This article aims to encourage four future actionable items: 1) the neurophysiologically accurate designation of, for example, "Hyperdopameism /Hyperdopameism" to replace the blaming nomenclature like alcoholism; 2) encouraging continued research into the nature of dysfunctional brainstem neurotransmitters across the brain reward circuitry; 3) early identification of people at risk for all RDS behaviors as a brain check (cognitive testing); 4) induction of dopamine homeostasis using "precision behavioral management" along with the coupling of GARS and precision Kb220 variants; 5) utilization of promising potential treatments include neuromodulating modalities such as Transmagnetic stimulation (TMS) and Deep Brain Stimulation(DBS), which target different areas of the neural circuitry involved in addiction and even neuroimmune agents like N-acetyl-cysteine.

摘要

奖赏缺乏综合征(RDS),尤其与成瘾性障碍相关,在全球造成了数十亿美元的损失,并在美国导致了超过100万人死亡。非法药物使用一直在稳步上升,2021年,美国12岁及以上的人群中,约21.9%(6120万)在过去一年中使用过非法药物。然而,这些人中只有1.5%(410万)接受过任何药物使用治疗。药物使用的增加以及未能对这些人进行充分治疗或提供治疗,导致2021年有106699人死于药物过量,且在2022年有所增加。本文提出了一种与基因导向疗法相关的替代性非药物治疗方法,这是数十年来的研究主题。这种范式转变的基石是大脑奖赏回路、脑干生理学以及由于遗传和表观遗传损伤对神经传递的相互关联级联以及腹侧被盖区 - 伏隔核(VTA - NAc)奖赏部位多巴胺的净释放所产生的影响而导致的神经递质缺陷。基因成瘾风险严重程度(GARS)测试和促多巴胺调节剂营养补充剂KB220相结合,以在整个大脑奖赏回路中诱导“多巴胺稳态”。本文旨在鼓励未来四项可采取行动的事项:1)例如,以神经生理学准确的名称“高多巴胺血症/高多巴胺血症”取代诸如酗酒等指责性术语;2)鼓励继续研究整个大脑奖赏回路中功能失调的脑干神经递质的性质;3)作为脑部检查(认知测试)早期识别所有RDS行为的高危人群;4)使用“精准行为管理”以及GARS和精准Kb220变体的结合来诱导多巴胺稳态;5)利用有前景的潜在治疗方法,包括针对成瘾所涉及神经回路不同区域的神经调节方式,如经颅磁刺激(TMS)和深部脑刺激(DBS),甚至像N - 乙酰半胱氨酸这样的神经免疫制剂。

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