Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety.
Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety.
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DOI：
10.1038/mp.2014.46
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发表时间：
2014-08
影响因子：
11
通讯作者：
Kalin, N. H.
中科院分区：
文献类型：
--
作者：
Birn, R. M.;Shackman, A. J.;Oler, J. A.;Williams, L. E.;McFarlin, D. R.;Rogers, G. M.;Shelton, S. E.;Alexander, A. L.;Pine, D. S.;Slattery, M. J.;Davidson, R. J.;Fox, A. S.;Kalin, N. H.
有些人天生就有一种生物学特性，使他们对新奇事物和潜在威胁更具反应性。当极端时，这种焦虑气质（AT）会增加焦虑，抑郁和药物滥用的风险。这些疾病是非常普遍的，衰弱，并可能是具有挑战性的treat. The高风险的AT表型表达类似的儿童和年轻的猴子和机械的工作表明，中央核（Ce）的杏仁核是一个重要的基板。虽然人们普遍认为，连接Ce和其他大脑区域的结构网络中的信息流是灵长类动物灵活调节焦虑的能力的基础，但对这个网络的功能结构仍然知之甚少。在这里，我们使用功能磁共振成像（fMRI）在麻醉的年轻猴子和安静休息的儿童焦虑症，以确定一个进化保守的模式的功能连接有关的早期生活的焦虑。在灵长类动物物种和意识水平中，背外侧前额叶皮层（dlPFC）之间的功能连接减少，该区域被认为在认知和情感控制中发挥核心作用，Ce与扫描仪外评估的焦虑增加有关。重要的是，高分辨率18-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）成像提供的证据表明，Ce代谢升高在统计学上介导了前额叶杏仁核连接和焦虑升高之间的关联。这些结果提供了有关极端早期焦虑的大脑网络的新线索，并为旨在开发改善儿科焦虑干预措施的机械工作奠定了基础。
Some individuals are endowed with a biology that renders them more reactive to novelty and potential threat. When extreme, this anxious temperament (AT) confers elevated risk for the development of anxiety, depression, and substance abuse. These disorders are highly prevalent, debilitating, and can be challenging to treat. The high-risk AT phenotype is expressed similarly in children and young monkeys and mechanistic work demonstrates that the central nucleus (Ce) of the amygdala is an important substrate. While it is widely believed that the flow of information across the structural network connecting the Ce to other brain regions underlies primates' capacity for flexibly regulating anxiety, the functional architecture of this network has remained poorly understood. Here we used functional magnetic resonance imaging (fMRI) in anesthetized young monkeys and quietly resting children with anxiety disorders to identify an evolutionarily-conserved pattern of functional connectivity relevant to early-life anxiety. Across primate species and levels of awareness, reduced functional connectivity between the dorsolateral prefrontal cortex (dlPFC), a region thought to play a central role in the control of cognition and emotion, and the Ce was associated with increased anxiety assessed outside the scanner. Importantly, high-resolution 18-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging provided evidence that elevated Ce metabolism statistically mediates the association between prefrontal-amygdalar connectivity and elevated anxiety. These results provide new clues about the brain network underlying extreme early-life anxiety and set the stage for mechanistic work aimed at developing improved interventions for pediatric anxiety.
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