Aepfelbacher Julia, Panny Benjamin, Price Rebecca B
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Biol Psychiatry Glob Open Sci. 2024 Apr 6;4(4):100316. doi: 10.1016/j.bpsgos.2024.100316. eCollection 2024 Jul.
Ketamine, an NMDA receptor antagonist, provides rapid antidepressant effects. Although much research has focused on neural and molecular mechanisms of action, it is critical to also consider psychological mechanisms that may contribute to its therapeutic efficacy. The construct of an awe-inducing experience, which is a well-validated psychological phenomenon tied to emotional well-being, had not been applied previously in ketamine research.
One hundred sixteen participants with depression, 77 of whom received a ketamine infusion (0.5 mg/kg over 40 minutes) and 39 patients who received saline placebo, completed a validated measure of awe (the Awe Experience Scale [AWE-S]) at 40 minutes postinfusion. AWE-S scores were examined as potential mediators of depression outcomes (% improvement in Montgomery-Åsberg Depression Rating Scale score) at 5 postinfusion time points (24 hours and 5, 12, 21, and 30 days). Dissociative effects, measured by Clinician-Administered Dissociative States Scale scores, were tested in parallel mediation models for comparison.
We found that the psychological experience of awe was strongly reported by participants during ketamine infusion, but not saline infusion, and there were significant associations between total AWE-S scores and Montgomery-Åsberg Depression Rating Scale score improvement (% change) in the ketamine arm at all 5 time points. Furthermore, at all 5 time points, total AWE-S scores statistically mediated the relationship between ketamine and Montgomery-Åsberg Depression Rating Scale scores. By contrast, Clinician-Administered Dissociative States Scale scores did not mediate outcomes at any time point.
Ketamine infusion strongly induced heightened feelings of awe, and these experiences consistently mediated depression outcomes over a 1- to 30-day period, unlike general dissociative side effects. The specific awe-inspiring properties of ketamine may contribute to its antidepressant effects.
氯胺酮作为一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，具有快速的抗抑郁作用。尽管许多研究聚焦于其神经和分子作用机制，但考虑可能对其治疗效果有贡献的心理机制也至关重要。敬畏诱发体验这一概念，是一种与情绪健康相关的经过充分验证的心理现象，此前尚未应用于氯胺酮研究。
116名抑郁症患者，其中77人接受氯胺酮静脉输注（40分钟内输注0.5mg/kg），39人接受生理盐水安慰剂，在输注后40分钟完成一项经过验证的敬畏测量（敬畏体验量表[AWE-S]）。在输注后5个时间点（24小时以及5、12、21和30天），将AWE-S得分作为抑郁结果（蒙哥马利-阿斯伯格抑郁评定量表得分改善百分比）的潜在中介因素进行检验。通过临床医生评定的分离状态量表得分测量的分离效应，在平行中介模型中进行检验以作比较。
我们发现，氯胺酮输注期间参与者强烈报告了敬畏的心理体验，而生理盐水输注期间则没有，并且在所有5个时间点，氯胺酮组的AWE-S总分与蒙哥马利-阿斯伯格抑郁评定量表得分改善（变化百分比）之间存在显著关联。此外，在所有5个时间点，AWE-S总分在统计学上介导了氯胺酮与蒙哥马利-阿斯伯格抑郁评定量表得分之间的关系。相比之下，临床医生评定的分离状态量表得分在任何时间点均未介导结果。
氯胺酮输注强烈诱发了增强的敬畏感，与一般的分离副作用不同，这些体验在1至30天的时间内持续介导抑郁结果。氯胺酮特定的敬畏诱发特性可能有助于其抗抑郁作用。
