Buckholtz J W, Callicott J H, Kolachana B, Hariri A R, Goldberg T E, Genderson M, Egan M F, Mattay V S, Weinberger D R, Meyer-Lindenberg A
Neuroimaging Core Facility, National Institute for Mental Health, NIH, DHHS, Bethesda, MD 20892-1365, USA.
Mol Psychiatry. 2008 Mar;13(3):313-24. doi: 10.1038/sj.mp.4002020. Epub 2007 May 22.
Little is known about neural mechanisms underlying human personality and temperament, despite their considerable importance as highly heritable risk mediators for somatic and psychiatric disorders. To identify these circuits, we used a combined genetic and imaging approach focused on Monoamine Oxidase A (MAOA), encoding a key enzyme for monoamine metabolism previously associated with temperament and antisocial behavior. Male carriers of a low-expressing genetic variant exhibited dysregulated amygdala activation and increased functional coupling with ventromedial prefrontal cortex (vmPFC). Stronger coupling predicted increased harm avoidance and decreased reward dependence scores, suggesting that this circuitry mediates a part of the association of MAOA with these traits. We utilized path analysis to parse the effective connectivity within this system, and provide evidence that vmPFC regulates amygdala indirectly by influencing rostral cingulate cortex function. Our data implicate a neural circuit for variation in human personality under genetic control, provide an anatomically consistent mechanism for vmPFC-amygdala interactions underlying this variation, and suggest a role for vmPFC as a superordinate regulatory area for emotional arousal and social behavior.
尽管人格和气质作为躯体疾病和精神疾病的高度可遗传风险调节因素具有相当重要的意义，但关于其潜在的神经机制却知之甚少。为了识别这些神经回路，我们采用了一种结合遗传学和影像学的方法，重点研究单胺氧化酶A（MAOA），它编码一种先前与气质和反社会行为相关的单胺代谢关键酶。低表达基因变异的男性携带者表现出杏仁核激活失调，以及与腹内侧前额叶皮层（vmPFC）的功能耦合增加。更强的耦合预示着回避伤害增加和奖赏依赖得分降低，这表明该神经回路介导了MAOA与这些特质之间关联的一部分。我们利用路径分析来解析该系统内的有效连接，并提供证据表明vmPFC通过影响喙扣带皮层功能间接调节杏仁核。我们的数据揭示了一个受基因控制的人类人格变异神经回路，为这种变异背后的vmPFC-杏仁核相互作用提供了解剖学上一致的机制，并表明vmPFC作为情绪唤醒和社会行为的上级调节区域发挥作用。
