New approaches to the neurobiology of posttraumatic stress disorder (PTSD) are needed to address the reported crisis in PTSD drug development. These new approaches may require the field to move beyond a narrow fear-based perspective, as fear-based medications have not yet demonstrated compelling efficacy. Antidepressants, particularly recent rapid-acting antidepressants, exert complex effects on brain function and structure that build on novel aspects of the biology of PTSD, including a role for stress-related synaptic dysconnectivity in the neurobiology and treatment of PTSD. Here, we integrate this perspective within a broader framework-in other words, a dual pathology model of ( a) stress-related synaptic loss arising from amino acid-based pathology and ( b) stress-related synaptic gain related to monoamine-based pathology. Then, we summarize the standard and experimental (e.g., ketamine) pharmacotherapeutic options for PTSD and discuss their putative mechanism of action and clinical efficacy.

中文翻译：

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创伤后应激障碍的神经生物学和药物治疗。

需要针对创伤后应激障碍 (PTSD) 的神经生物学采取新方法来解决所报告的 PTSD 药物开发危机。这些新方法可能要求该领域超越狭隘的基于恐惧的视角，因为基于恐惧的药物尚未表现出令人信服的功效。抗抑郁药，特别是最近的速效抗抑郁药，对大脑功能和结构产生复杂的影响，这些影响建立在 PTSD 生物学的新方面，包括压力相关的突触连接障碍在神经生物学和 PTSD 治疗中的作用。在这里，我们将这一观点整合到更广泛的框架中，换句话说，这是一个双重病理学模型：（a）由基于氨基酸的病理学引起的与压力相关的突触损失和（b）与基于单胺的病理学相关的压力相关的突触增益。然后，我们总结了 PTSD 的标准和实验（例如氯胺酮）药物治疗方案，并讨论了它们的假定作用机制和临床疗效。