Anxiety disorders are among the most prevalent psychiatric disorders, causing significant suffering and disability. Behavioral inhibition is a temperament that is linked to an increased risk for the later development of anxiety disorders and other stress-related psychopathology, and understanding the neural systems underlying this dispositional risk could provide insight into novel treatment targets for anxiety disorders. Nonhuman primates (NHPs) have anxiety-related temperaments that are similar to those of humans with behavioral inhibition, facilitating the design of translational models related to human psychopathology. Characterization of our NHP model of behavioral inhibition, which we term anxious temperament (AT), reveals that it is trait-like. Exploration of the neural substrates of AT in NHPs has revealed a distributed neural circuit that is linked to individual differences in AT, which includes the dorsal amygdala. AT-related metabolism in the dorsal amygdala, including the central nucleus, is stable across time and can be detected even in safe contexts, suggesting that AT has trait-like neural signatures within the brain. The use of lesioning and novel chemogenetic methods allows for mechanistic perturbation of the amygdala to determine its causal contribution to AT. Studies characterizing the molecular bases for individual differences in AT in the dorsal amygdala, which take advantage of novel methods for probing cellular and molecular systems, suggest involvement of neurotrophic systems, which point to the importance of neuroplasticity in AT. These novel methods, when used in combination with translational NHP models such as AT, promise to provide insights into the brain systems underlying the early risk for anxiety disorder development.

中文翻译：

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非人类灵长类动物模型探索生命早期气质焦虑的潜在机制

焦虑症是最普遍的精神疾病之一，会导致严重的痛苦和残疾。行为抑制是一种气质，与焦虑症和其他与压力相关的精神病理学的后期发展风险增加有关，了解这种倾向性风险背后的神经系统可以深入了解焦虑症的新治疗目标。非人类灵长类动物 (NHP) 具有与具有行为抑制的人类相似的焦虑相关气质，这有助于设计与人类精神病理学相关的转化模型。我们的 NHP 行为抑制模型的特征，我们称之为焦虑气质 (AT)，表明它是类似特质的。对 NHP 中 AT 神经基质的探索揭示了一个分布式神经回路，该回路与 AT 的个体差异有关，其中包括背侧杏仁核。背侧杏仁核（包括中央核）中与 AT 相关的代谢随着时间的推移是稳定的，即使在安全的环境中也可以检测到，这表明 AT 在大脑内具有类似特征的神经特征。损伤和新的化学遗传学方法的使用允许杏仁核的机械扰动来确定其对 AT 的因果贡献。研究表征了背侧杏仁核中 AT 个体差异的分子基础，这些研究利用了探索细胞和分子系统的新方法，表明神经营养系统的参与，这表明了 AT 中神经可塑性的重要性。这些新颖的方法，