Volavka Jan, Bilder Robert, Nolan Karen
Nathan Kline Institute, 140 Old Orangeburg Road, Orangeburg, New York 10962, USA.
Ann N Y Acad Sci. 2004 Dec;1036:393-8. doi: 10.1196/annals.1330.023.
Catecholaminergic systems are involved in the regulation of aggressive behavior; this regulation is implemented in interactions with other neurobiological mechanisms. Most of the available evidence indicates that norepinephrine and dopamine lower the threshold for an aggressive response to environmental stimuli. Two major enzymes are responsible for catecholamine catabolism in the brain: catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA). The transcriptional activity of the genes coding for these enzymes is governed by common functional polymorphisms. If aggressive behavior is enhanced by catecholaminergic activity, then the lower activity of COMT and MAOA (resulting in a slower inactivation of catecholamines) should indirectly enhance aggression. This prediction has been supported by most (but not all) observations in rodents and humans. Male mice that have either the COMT or the MAOA gene knocked out show elevated aggression. The allele that codes for the lower enzymatic activity of COMT has been associated with elevated aggressive behavior in several samples of psychiatric patients. Similarly, the alleles that code for the lower activity of MAOA were associated with the development of aggressive behavior in maltreated male children in a large birth cohort study. Collectively, these results suggest that COMT and MAOA polymorphisms represent a basic neurobiological mechanism that contributes to the regulation of aggressive behavior.
儿茶酚胺能系统参与攻击行为的调节；这种调节是在与其他神经生物学机制的相互作用中实现的。现有大部分证据表明，去甲肾上腺素和多巴胺会降低对环境刺激产生攻击反应的阈值。大脑中负责儿茶酚胺分解代谢的有两种主要酶：儿茶酚-O-甲基转移酶（COMT）和单胺氧化酶A（MAOA）。编码这些酶的基因的转录活性受常见功能多态性的控制。如果攻击行为因儿茶酚胺能活性增强而增加，那么COMT和MAOA活性降低（导致儿茶酚胺失活减慢）应会间接增强攻击性。这一预测在啮齿动物和人类的大多数（但并非全部）观察结果中得到了支持。敲除了COMT或MAOA基因的雄性小鼠表现出攻击性增强。在几个精神病患者样本中，编码COMT较低酶活性的等位基因与攻击行为增加有关。同样，在一项大型出生队列研究中，编码MAOA较低活性的等位基因与受虐待男性儿童攻击行为的发展有关。总体而言，这些结果表明，COMT和MAOA多态性代表了一种有助于调节攻击行为的基本神经生物学机制。
