Center for the Neurobiology of Stress Resilience and Psychiatric Disorders, Discipline of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, USA.
Neuropharmacology. 2023 Jul 1;232:109529. doi: 10.1016/j.neuropharm.2023.109529. Epub 2023 Mar 31.
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.
目前用于治疗焦虑症和创伤后应激障碍（PTSD）的药物疗效有限，但自 20 世纪 80 年代以来，尚无新的抗焦虑药物获批用于治疗。在本期《神经药理学》的“恐惧、焦虑和 PTSD：从细胞机制到转化方法”中，我们综述了目前推荐用于 PTSD 的药物治疗，并讨论了正在重新评估或新开发的有前途的药物治疗方法。PTSD 治疗药物的新策略包括使用血清素能致幻剂作为低剂量辅助治疗与心理治疗相结合。我们还讨论了使用糖皮质激素靶向创伤暴露后不久的时间窗口，以干扰恐惧记忆的巩固。尽管许多因素阻碍了焦虑症和 PTSD 药物治疗的发展，但我们强调以下三个因素：（1）尽管女性焦虑症的患病率较高，但研究女性动物模型恐惧处理神经生物学的临床前研究很少；（2）关于压力如何影响整个生命周期中恐惧回路发育的知识在临床实践中的应用较差；（3）我们对适应性和适应性恐惧处理中的经典恐惧回路的了解甚少。最后，我们强调了内脏感觉信号与情绪调节之间的功能联系，并讨论了这些内脏感觉信号如何成为 PTSD 治疗的切入点，因为 PTSD 通常伴随着心血管失调。更好地理解适应性和适应性恐惧处理的神经生物学基础对于确定风险因素至关重要，这些风险因素将推动针对性别和发育性创伤的干预措施的发展，为焦虑症和 PTSD 带来精准医学的新时代。
