Laboratory of Molecular Biology, Department of Surgical, Medical and Molecular Pathology and of Critical Care, University of Pisa, Pisa I-56126, Italy.
Laboratory of Molecular Biology, Department of Surgical, Medical and Molecular Pathology and of Critical Care, University of Pisa, Pisa I-56126, Italy
Exp Biol Med (Maywood). 2014 Nov;239(11):1514-23. doi: 10.1177/1535370214529508. Epub 2014 Apr 24.
Over the last two decades, it has become increasingly evident that control of aggressive behavior is modulated by the individual genetic profile as well. Several candidate genes have been proposed to play a role in the risk to develop antisocial behavior, and distinct brain imaging studies have shown that specific cortical areas may be functionally and/or structurally impaired in impulsive violent subjects on the basis of their genotypes. In this paper, we review the findings regarding four polymorphisms-MAOA (Monoamine oxidase A) uVNTR, SLC6A4 (solute carrier family 6 (neurotransmitter transporter), member 4) 5HTTLPR, COMT (Catechol-O-methyltransferase) Val158Met and DRD4 (dopamine D4 receptor) VNTR 1-11-that all have been found to be associated with an increased vulnerability for antisocial and impulsive behavior in response to aversive environmental conditions. These results, however, have not been replicated by other studies, likely because of crucial methodological discrepancies, including variability in the criteria used to define antisocial behavior and assessment of environmental factors. Finally, it has been recently proposed that these genetic variants may actually increase the individual susceptibility not merely to the negative environmental factors, but to the positive ones as well. In this view, such alleles would play a wider modulatory role, by acting as "plasticity" rather than "vulnerability" genes. Overall, these findings have potential important implications that span well outside of neuroscience and psychiatry, to embrace ethics, philosophy, and the law itself, as they pose new challenges to the very notion of Free Will. Novel properly controlled studies that examine multi-allelic genetic profiles, rather than focusing on distinct single variants, will make it possible to achieve a clearer understanding of the molecular underpinnings of the nature by nurture interaction.
在过去的二十年中，越来越明显的是，个体的遗传特征也可以调节攻击性行为的控制。有几个候选基因被提出在发展反社会行为的风险中起作用，而不同的脑成像研究表明，基于特定的基因型，特定的皮质区域可能在冲动暴力个体中存在功能和/或结构上的损伤。在本文中，我们回顾了四个多态性的发现-MAOA（单胺氧化酶 A）uVNTR、SLC6A4（溶质载体家族 6（神经递质转运体），成员 4）5HTTLPR、COMT（儿茶酚-O-甲基转移酶）Val158Met 和 DRD4（多巴胺 D4 受体）VNTR 1-11-所有这些多态性都与对厌恶环境条件的反社会和冲动行为的易感性增加有关。然而，这些结果并没有被其他研究复制，这可能是由于关键的方法差异，包括用于定义反社会行为的标准和环境因素评估的可变性。最后，最近有人提出，这些遗传变异实际上可能不仅增加了个体对负面环境因素的易感性，而且增加了对正面环境因素的易感性。在这种观点下，这些等位基因将通过充当“可塑性”而不是“脆弱性”基因，发挥更广泛的调节作用。总的来说，这些发现具有潜在的重要意义，不仅跨越了神经科学和精神病学，还包括伦理、哲学和法律本身，因为它们对自由意志的概念提出了新的挑战。进行适当控制的新研究，检查多等位基因遗传特征，而不是专注于不同的单一变异，将有可能更清楚地了解基因与环境相互作用的分子基础。
