›› 2020, Vol. 43 ›› Issue (1): 224-231.

• 临床与咨询 • 上一篇    下一篇

恐惧记忆习得与消退的性别差异及其神经机制

杨勇,李俊娇,陈伟,胡琰健,曹杨婧文,竭婧,郑希付   

  1. 华南师范大学
  • 收稿日期:2018-10-20 修回日期:2019-05-05 出版日期:2020-01-15 发布日期:2020-01-20
  • 通讯作者: 郑希付

Sex Difference and Its Neural Underpinnings in Fear Acquisition and Extinction

  • Received:2018-10-20 Revised:2019-05-05 Online:2020-01-15 Published:2020-01-20
  • Contact: Fu XiZheng

摘要: 大多数人在其一生中都会经历创伤事件,但只有少数人会发展成为创伤后应激障碍(PTSD)。焦虑障碍的易感性和保护因素成为一个重要议题。基于恐惧记忆习得与消退模型的研究发现女性个体表现出“易习得、难消退”的特点。在恐惧相关脑区的脑生理结构、功能/结构连接性、以及大脑可塑性的性别差异可能是该特征的根本原因。性激素作为一种焦虑障碍的保护因素,可以调节这种性别差异,这种调节效应可能是通过影响大脑结构形态(如神经细胞的形态和数量)、调控与记忆相关基因的表达(如HDAC4)而实现的。雌性激素水平的不稳定性可能是女性易感焦虑障碍的重要原因。未来对性别差异的深入研究将有助于推进个性化医疗。

关键词: 性别差异, PTSD, 性激素, 恐惧记忆, 恐惧消退

Abstract: Abstract: Most people have experienced traumatic events throughout their lives, but only a few developed into Posttraumatic Stress Disorder (PTSD). The susceptibility and protective factors of anxiety disorders have become an important issue. Maladaptive memories are considered to be the main cause of some mental disorders, such as Posttraumatic Stress Disorder (PTSD), and thus it became the main target in treatment. Exposure therapy is considered to be one of the most effective interventions for PTSD. The acquisition and extinction model of fear memory has been successfully used to model the exposure therapy of PTSD in the laboratory. Based on the acquisition and extinction model of fear memory, it was found that the female, compared to the male, showed the characteristics of " easier to learn and more difficult to fade". To be more specific, the female showed faster acquisition of fear memory than the male; on the contrary, they had to need more time or trails to eliminate the fear response to the conditioned stimuli than the male during the extinction phase. What’s more, compared to the male, fear relapse are more common in the female even after successfully eliminate the fear response to the conditioned stimuli by extinction procedure. Although few studies explored the neural mechanisms behind these sex differences in the acquisition and extinction of fear memory, the existing studies have shown that there are significant sex differences in the physiological structure, structural or functional connectivity between these regions, as well as the brain plasticity, of fear-related brain regions (such as the amygdala, the prefrontal cortex and cingulate cortex and hippocampus, etc.). These sex differences in the neural network of fear memories would be the true cause of the characteristics of "easier to learn and more difficult to fade" showed in the acquisition and extinction of fear memory. Meanwhile, the gonadal hormones as a kind of protective factors of anxiety disorders, they can regulate the sex differences in the acquisition and extinction of fear memory, which may be achieved through regulating the effects of acute/ chronic stress or trauma exposure on the formation of brain structure (such as nerve cells morphology and nerve cells quantity of amygdala), and regulating the expression of genes associated with fear memory (e.g., HDAC4). The instability of estrogen levels may be an important reason for the more susceptibility to anxiety disorders in the female. Finally, it's important to note that the researches on sex differences in anxiety disorders are still very scarce, and there are many questions that deserve more in-depth research in the future. The studies of sex differences in anxiety disorders are of great importance to optimize treatment in the clinical context because it is the first step to realize individualized medicine. Thus, more efforts need to be done for exploring the protective mechanism of gonadal hormones, trying to use sex hormones as an adjuvant therapy to improve the symptoms of PTSD, and the sex differences in the boundary conditions of opening resonsolidation window of fear memories in the future.

Key words: Sex difference, PTSD, Gonadal hormones, Fear memory, Fear extinction