State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Front Med. 2022 Aug;16(4):518-539. doi: 10.1007/s11684-022-0941-2. Epub 2022 Aug 9.
Pathological anxiety is among the most difficult neuropsychiatric diseases to treat pharmacologically, and it represents a major societal problem. Studies have implicated structural changes within the prefrontal cortex (PFC) and functional changes in the communication of the PFC with distal brain structures in anxiety disorders. Treatments that affect the activity of the PFC, including cognitive therapies and transcranial magnetic stimulation, reverse anxiety- and fear-associated circuit abnormalities through mechanisms that remain largely unclear. While the subjective experience of a rodent cannot be precisely determined, rodent models hold great promise in dissecting well-conserved circuits. Newly developed genetic and viral tools and optogenetic and chemogenetic techniques have revealed the intricacies of neural circuits underlying anxiety and fear by allowing direct examination of hypotheses drawn from existing psychological concepts. This review focuses on studies that have used these circuit-based approaches to gain a more detailed, more comprehensive, and more integrated view on how the PFC governs anxiety and fear and orchestrates adaptive defensive behaviors to hopefully provide a roadmap for the future development of therapies for pathological anxiety.
病理性焦虑是最难用药物治疗的神经精神疾病之一，也是一个主要的社会问题。研究表明，在焦虑障碍中，前额叶皮层（PFC）的结构变化和 PFC 与远端脑结构的通讯功能变化有关。影响 PFC 活动的治疗方法，包括认知疗法和经颅磁刺激，通过在很大程度上尚不清楚的机制来逆转与焦虑和恐惧相关的回路异常。虽然无法准确确定啮齿动物的主观体验，但啮齿动物模型在剖析高度保守的回路方面具有很大的潜力。新开发的遗传和病毒工具以及光遗传学和化学遗传学技术通过允许直接检验从现有心理概念中得出的假设，揭示了焦虑和恐惧背后的神经回路的复杂性。本综述重点介绍了使用这些基于回路的方法的研究，以更详细、更全面、更综合地了解 PFC 如何控制焦虑和恐惧，并协调适应性防御行为，希望为病理性焦虑的治疗方法的未来发展提供路线图。
