Su Tung-Ping, Cheng Li-Kai, Tu Pei-Chi, Chen Li-Fen, Lin Wei-Chen, Li Cheng-Ta, Bai Ya-Mei, Tsai Shih-Jen, Chen Mu-Hong
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Psychiatry, General Cheng Hsin Hospital, Taipei, Taiwan.
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Psychiatry Res. 2025 Mar;345:116377. doi: 10.1016/j.psychres.2025.116377. Epub 2025 Jan 26.
Ketamine is a dissociative drug used for the treatment of depression. However, the neurofunctional mechanism underlying the antidepressant effect of ketamine remains unknown. According to previous research, low-dose ketamine affects large-scale brain networks, including default-mode and salient networks.
A total of 43 patients with treatment-resistant depression (TRD) and suicidal ideation (SI) were randomly assigned to receive a single infusion of either 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. Depressive and suicidal symptoms were evaluated using the 17-item Hamilton Depression Rating Scale and the Columbia-Suicide Severity Rating Scale: Ideation Severity Subscale. Resting-state functional magnetic resonance imaging was performed at baseline and on day 3 after infusion. Graph theoretic metrics such as degree centrality and clustering coefficient were examined.
Relative to midazolam use, low-dose ketamine infusion reduced depressive (p = 0.001) and suicidal (p = 0.025) symptoms and improved the brain network integrity, including increased degree centrality and clustering coefficient in the angular gyrus and increased degree centrality in the right thalamus.
Neurofunctional changes in the thalamus and default-mode network (angular gyrus) may be associated with the antidepressant effect of ketamine on patients with TRD and SI.
UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000033916.
氯胺酮是一种用于治疗抑郁症的解离性药物。然而，氯胺酮抗抑郁作用的神经功能机制尚不清楚。根据先前的研究，低剂量氯胺酮会影响大规模脑网络，包括默认模式网络和突显网络。
总共43例难治性抑郁症（TRD）伴自杀观念（SI）患者被随机分配接受单次输注0.5mg/kg氯胺酮或0.045mg/kg咪达唑仑。使用17项汉密尔顿抑郁量表和哥伦比亚自杀严重程度评定量表：观念严重程度分量表评估抑郁和自杀症状。在基线和输注后第3天进行静息态功能磁共振成像。检查了诸如度中心性和聚类系数等图论指标。
相对于使用咪达唑仑，低剂量氯胺酮输注减轻了抑郁（p = 0.001）和自杀（p = 0.025）症状，并改善了脑网络完整性，包括角回的度中心性和聚类系数增加以及右侧丘脑的度中心性增加。
丘脑和默认模式网络（角回）的神经功能变化可能与氯胺酮对TRD和SI患者的抗抑郁作用有关。
UMIN临床试验注册中心（UMIN-CTR）：注册号：UMIN000033916。
