Berkowitz Rachel Lisa, Coplan Jeremy D, Reddy Dorothy P, Gorman Jack M
Department of Psychiatry, College of Physicians and Surgeons of Columbia University, Brooklyn, NY, USA.
Rev Neurosci. 2007;18(3-4):191-207. doi: 10.1515/revneuro.2007.18.3-4.191.
Numerous studies suggest that the amygdala is critical for the acquisition and expression of fear. Conditioned fear in animals has been considered a good model for human anxiety disorders, but animal models of anxiety have several limitations. Conditioned fear in animals can be directed to a specific stressor and is easily extinguished. Furthermore, animals do not seem to be able to develop the capacity to worry excessively about the future. While animal models are useful and can demonstrate psychiatric illnesses, they do not completely mimic the complex cognitive processes that occur in anxious humans. Thus, we hypothesize that human anxiety disorders are caused at least in part by differential activity in the prefrontal cortex, the brain region that most separates us from our nearest genetic neighbors. The human prefrontal cortex has not only been shown to be more developed than that of other mammals, but it also has unique morphology and gene expression. Neuroimaging studies repeatedly show abnormalities in the prefrontal cortex in anxious individuals. Thus, we suggest that the very same cortical complexity that allows us to produce a vibrant culture is also the seat of anxiety disorders. Interestingly, preclinical studies have shown that the prefrontal cortex inhibits the amygdala. There appears to be a distinction between two classes of anxiety disorders. Those disorders involving intense fear and panic--panic disorder, post-traumatic stress disorder, and phobias--seem to be characterized by an underactivity of the prefrontal cortex, thus disinhibiting the amygdala. Disorders such as generalized anxiety disorder and obsessive-compulsive disorder, which involve worry and rumination, on the other hand, seem to be characterized by an overactivity of the prefrontal cortex. Studies of prefrontal cortical function in psychiatric illness should be a fruitful method for identifying effective treatment approaches.
大量研究表明，杏仁核对于恐惧的习得和表现至关重要。动物的条件性恐惧被认为是人类焦虑症的良好模型，但焦虑症的动物模型存在若干局限性。动物的条件性恐惧可以针对特定的应激源，并且很容易消退。此外，动物似乎无法培养出过度担忧未来的能力。虽然动物模型很有用，能够展示精神疾病，但它们并不能完全模拟焦虑的人类所发生的复杂认知过程。因此，我们推测人类焦虑症至少部分是由前额叶皮质的不同活动引起的，前额叶皮质是使我们与最近的基因邻居最有区别的脑区。人类的前额叶皮质不仅比其他哺乳动物的更发达，而且具有独特的形态和基因表达。神经影像学研究反复表明，焦虑个体的前额叶皮质存在异常。因此，我们认为，正是这种使我们能够创造充满活力的文化的皮质复杂性，也是焦虑症的根源。有趣的是，临床前研究表明，前额叶皮质会抑制杏仁核。两类焦虑症之间似乎存在区别。那些涉及强烈恐惧和惊恐的疾病——惊恐障碍、创伤后应激障碍和恐惧症——似乎以前额叶皮质活动不足为特征，从而解除了对杏仁核的抑制。另一方面，诸如广泛性焦虑症和强迫症等涉及担忧和沉思的疾病，似乎以前额叶皮质活动过度为特征。对精神疾病中前额叶皮质功能的研究应该是确定有效治疗方法的富有成效的方法。
