Meyer-Lindenberg Andreas, Buckholtz Joshua W, Kolachana Bhaskar, R Hariri Ahmad, Pezawas Lukas, Blasi Giuseppe, Wabnitz Ashley, Honea Robyn, Verchinski Beth, Callicott Joseph H, Egan Michael, Mattay Venkata, Weinberger Daniel R
Unit for Systems Neuroscience in Psychiatry, Neuroimaging Core Facility, National Institutes of Health, Department of Health and Human Services, 9000 Rockville Pike, Bethesda, MD 20892-1365, USA.
Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6269-74. doi: 10.1073/pnas.0511311103. Epub 2006 Mar 28.
Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functional polymorphism in MAOA on brain structure and function assessed with MRI in a large sample of healthy human volunteers. We show that the low expression variant, associated with increased risk of violent behavior, predicted pronounced limbic volume reductions and hyperresponsive amygdala during emotional arousal, with diminished reactivity of regulatory prefrontal regions, compared with the high expression allele. In men, the low expression allele is also associated with changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during aversive recall, and impaired cingulate activation during cognitive inhibition. Our data identify differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression, suggest neural systems-level effects of X-inactivation in human brain, and point toward potential targets for a biological approach toward violence.
导致人类暴力行为的神经生物学因素仍未得到充分理解。解决这个问题的一种方法是研究X连锁单胺氧化酶A（MAOA）基因的等位基因变异，该基因先前已被证明与动物和人类的冲动攻击性有关。在此，我们研究了MAOA基因中一种常见功能多态性对大脑结构和功能的影响，使用MRI对大量健康人类志愿者样本进行了评估。我们发现，与暴力行为风险增加相关的低表达变异体，与高表达等位基因相比，在情绪唤起期间预测了明显的边缘脑区体积减少和杏仁核反应过度，同时调节性前额叶区域的反应性降低。在男性中，低表达等位基因还与厌恶回忆期间眶额体积变化、杏仁核和海马反应过度以及认知抑制期间扣带回激活受损有关。我们的数据确定了边缘脑区在情绪调节和认知控制方面的差异，这些差异可能与MAOA基因和冲动攻击性之间的关联有关，提示了人类大脑中X染色体失活的神经系统水平效应，并指出了暴力行为生物学研究方法的潜在靶点。
