Department of Fundamental and Applied Neurobiology, Serbsky State Research Center of Forensic and Social Psychiatry, Kropotkinsky Pereulok 23, Moscow, Russia.
J Appl Genet. 2012 Feb;53(1):61-82. doi: 10.1007/s13353-011-0069-6. Epub 2011 Oct 13.
Human aggression/impulsivity-related traits have a complex background that is greatly influenced by genetic and non-genetic factors. The relationship between aggression and anxiety is regulated by highly conserved brain regions including amygdala, which controls neural circuits triggering defensive, aggressive, or avoidant behavioral models. The dysfunction of neural circuits responsible for emotional control was shown to represent an etiological factor of violent behavior. In addition to the amygdala, these circuits also involve the anterior cingulated cortex and regions of the prefrontal cortex. Excessive reactivity in the amygdala coupled with inadequate prefrontal regulation serves to increase the likelihood of aggressive behavior. Developmental alterations in prefrontal-subcortical circuitry as well as neuromodulatory and hormonal abnormality appear to play a role. Imbalance in testosterone/serotonin and testosterone/cortisol ratios (e.g., increased testosterone levels and reduced cortisol levels) increases the propensity toward aggression because of reduced activation of the neural circuitry of impulse control and self-regulation. Serotonin facilitates prefrontal inhibition, and thus insufficient serotonergic activity can enhance aggression. Genetic predisposition to aggression appears to be deeply affected by the polymorphic genetic variants of the serotoninergic system that influences serotonin levels in the central and peripheral nervous system, biological effects of this hormone, and rate of serotonin production, synaptic release and degradation. Among these variants, functional polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (5-HTT) may be of particular importance due to the relationship between these polymorphic variants and anatomical changes in the limbic system of aggressive people. Furthermore, functional variants of MAOA and 5-HTT are capable of mediating the influence of environmental factors on aggression-related traits. In this review, we consider genetic determinants of human aggression, with special emphasis on genes involved in serotonin and dopamine metabolism and function.
人类的攻击/冲动相关特质具有复杂的背景，受遗传和非遗传因素的影响很大。攻击与焦虑之间的关系受到高度保守的大脑区域的调节，包括控制触发防御性、攻击性或回避性行为模式的神经回路的杏仁核。负责情绪控制的神经回路功能障碍被证明是暴力行为的一个病因因素。除了杏仁核，这些回路还涉及前扣带皮层和前额叶皮层的区域。杏仁核过度反应与前额叶调节不足相结合，增加了攻击行为的可能性。前额叶-皮质下回路的发育改变以及神经调质和激素异常似乎也起作用。睾酮/血清素和睾酮/皮质醇比值的不平衡（例如，睾酮水平升高和皮质醇水平降低）会增加攻击倾向，因为冲动控制和自我调节的神经回路的激活减少。血清素促进前额叶抑制，因此血清素活动不足会增强攻击行为。攻击的遗传倾向似乎受到影响中枢和外周神经系统中血清素水平、这种激素的生物学效应以及血清素产生、突触释放和降解速度的血清素能系统多态性遗传变异的深刻影响。在这些变体中，单胺氧化酶 A（MAOA）和 5-羟色胺转运体（5-HTT）的功能性多态性可能特别重要，因为这些多态性变体与攻击性个体边缘系统的解剖变化有关。此外，MAOA 和 5-HTT 的功能变体能够介导环境因素对与攻击相关特质的影响。在这篇综述中，我们考虑了人类攻击的遗传决定因素，特别强调了涉及 5-羟色胺和多巴胺代谢和功能的基因。
