Exploration of Epigenetic State Hyperdopaminergia (Surfeit) and Genetic Trait Hypodopaminergia (Deficit) During Adolescent Brain Development.

Kenneth Blum, Abdalla Bowirrat, Marjorie C Gondre Lewis, Thomas A Simpatico, Mauro Ceccanti, Bruce Steinberg, Edward J Modestino, Panayotis K Thanos, David Baron, Thomas McLaughlin, Raymond Brewer, Rajendra D Badgaiyan, Jessica Valdez Ponce, Lisa Lott, Mark S Gold
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Abstract

Background: The risk for all addictive drug and non-drug behaviors, especially, in the unmyelinated Prefrontal Cortex (PFC) of adolescents, is important and complex. Many animal and human studies show the epigenetic impact on the developing brain in adolescents, compared to adults. Some reveal an underlying hyperdopaminergia that seems to set our youth up for risky behaviors by inducing high quanta pre-synaptic dopamine release at reward site neurons. In addition, altered reward gene expression in adolescents caused epigenetically by social defeat, like bullying, can continue into adulthood. In contrast, there is also evidence that epigenetic events can elicit adolescent hypodopaminergia. This complexity suggests that neuroscience cannot make a definitive claim that all adolescents carry a hyperdopaminergia trait.

Objective: The primary issue involves the question of whether there exists a mixed hypo or hyper-dopaminergia in this population.

Method: Genetic Addiction Risk Score (GARS®) testing was carried out of 24 Caucasians of ages 12-19, derived from families with RDS.

Results: We have found that adolescents from this cohort, derived from RDS parents, displayed a high risk for any addictive behavior (a hypodopaminergia), especially, drug-seeking (95%) and alcohol-seeking (64%).

Conclusion: The adolescents in our study, although more work is required, show a hypodopaminergic trait, derived from a family with Reward Deficiency Syndrome (RDS). Certainly, in future studies, we will analyze GARS in non-RDS Caucasians between the ages of 12-19. The suggestion is first to identify risk alleles with the GARS test and, then, use well-researched precision, pro-dopamine neutraceutical regulation. This "two-hit" approach might prevent tragic fatalities among adolescents, in the face of the American opioid/psychostimulant epidemic.

探索青少年大脑发育过程中的表观遗传状态多巴胺功能亢进症(过剩)和遗传特质多巴胺功能亢进症(不足)。
背景:所有成瘾性药物和非药物行为的风险,尤其是青少年未髓鞘化的前额叶皮层(PFC)的风险,都是重要而复杂的。许多动物和人体研究表明,与成年人相比,青少年大脑发育过程中的表观遗传学影响很大。一些研究揭示了一种潜在的多巴胺亢进症,它似乎通过诱导奖赏部位神经元的高量突触前多巴胺释放,为青少年的危险行为埋下了伏笔。此外,社会挫败(如欺凌)在青少年中造成的表观遗传学上的奖赏基因表达改变可能会持续到成年。与此相反,也有证据表明,表观遗传事件可导致青少年多巴胺功能减退。这种复杂性表明,神经科学无法明确断言所有青少年都具有多巴胺功能亢进症的特质:首要问题是,在这一人群中是否存在混合性多巴胺功能减退症或多巴胺功能亢进症:方法:对来自RDS家庭的24名12-19岁的白种人进行了遗传成瘾风险评分(GARS®)测试:结果:我们发现,来自 RDS 父母家庭的青少年有较高的成瘾行为风险(多巴胺功能减退),尤其是寻求毒品(95%)和酒精(64%):结论:尽管还需要做更多的工作,但我们研究中的青少年表现出了低多巴胺能特征,这种特征来自于一个奖赏缺失综合症(RDS)家族。当然,在今后的研究中,我们将对 12-19 岁非奖赏缺失综合征高加索人的 GARS 进行分析。我们的建议是,首先通过 GARS 测试确定风险等位基因,然后再使用经过充分研究的精确的促多巴胺中性调节剂。面对美国阿片类药物/精神兴奋剂的流行,这种 "一箭双雕 "的方法或许能避免青少年死亡悲剧的发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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