From recent advances in underlying neurocircuitry of fear and anxiety to promising pharmacotherapies for PTSD: The saga of heart, sex and the developing brain.
From recent advances in underlying neurocircuitry of fear and anxiety to promising pharmacotherapies for PTSD: The saga of heart, sex and the developing brain.
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从恐惧和焦虑的潜在神经回路的最新进展到有前景的创伤后应激障碍药物疗法：心脏、性和大脑发育的传奇。
DOI：
10.1016/j.neuropharm.2023.109529
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发表时间：
2023
影响因子：
4.7
通讯作者：
Dabrowska,Joanna
中科院分区：
文献类型：
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作者：
Dabrowska,Joanna
现有的治疗焦虑症和创伤后应激障碍（PTSD）的药物治疗效果有限，但自20世纪80年代以来，没有新的抗焦虑药物被批准用于治疗。在本期神经药理学“恐惧、焦虑和创伤后应激障碍：从细胞机制到转化方法”中，我们回顾了目前推荐的创伤后应激障碍药物治疗方法，并讨论了正在重新研究或新开发的有前途的药物治疗方法。创伤后应激障碍药物治疗的新策略包括使用5 -羟色胺类致幻剂作为低剂量的辅助治疗与心理治疗相结合。我们还讨论了在创伤暴露后不久，糖皮质激素靶向颞窗的使用，以干扰恐惧记忆的巩固。尽管许多因素阻碍了焦虑症和创伤后应激障碍药物治疗的发展，但我们强调了三个方面：(1)尽管女性焦虑障碍的患病率较高，但在女性动物模型中调查恐惧加工神经生物学的临床前研究较少；(2)在临床实践中对压力如何影响恐惧回路发展的了解很少；(3)我们缺乏对适应与非适应恐惧加工中典型恐惧回路的了解。最后，我们强调了内感受性信号与情绪调节之间的功能联系，并讨论了这些内感受性信号如何可能成为创伤后应激障碍治疗的一个途径，创伤后应激障碍通常伴有心血管失调。更好地理解适应和不适应恐惧处理的神经生物学基础，对于识别风险因素至关重要，这些因素将刺激针对性和发育性创伤的干预措施的发展，开创一个针对焦虑症和创伤后应激障碍的精准医学的新时代。
Available pharmacotherapies for anxiety disorders and post-traumatic stress-disorder (PTSD) have limited efficacy, but no new anxiolytic drug has been approved for treatment since the 1980s. In this issue of Neuropharmacology on “Fear, anxiety and PTSD: from cellular mechanisms to translational approaches”, we review the currently recommended pharmacotherapy for PTSD and discuss promising pharmacotherapies being revisited or newly developed. Novel strategies for pharmaceuticals in PTSD treatment include the use of serotonergic psychedelics as low-dose adjunct therapies combined with psychotherapy. We also discuss the use of glucocorticoids targeting the temporal window shortly following trauma exposure to interfere with fear memory consolidation. Although many factors have impeded progress in pharmacotherapy development for anxiety disorders and PTSD, we highlight three: (1) the sparsity of preclinical studies investigating the neurobiology of fear processing in female animal models despite the higher prevalence of anxiety disorders in women, (2) the poor implementation of the knowledge of how stress affects fear circuitry development across the lifetime into clinical practice, and (3) our paucity of knowledge of canonical fear circuitry in adaptive vs. maladaptive fear processing. Finally, we emphasize the functional link between interoceptive signals and emotion regulation and discuss how these interoceptive signals may be an inroad into PTSD treatment, which is often accompanied by cardiovascular dysregulation. A better understanding of the neurobiological underpinnings of adaptive and maladaptive fear processing is critical for identifying risk factors that will spur the development of sex- and developmental trauma-specific interventions, ushering in a new era of precision medicine for anxiety disorders and PTSD.