Chen Mu-Hong, Su Tung-Ping, Chen Li-Fen, Li Cheng-Ta, Wu Hui-Ju, Lin Wei-Chen, Tsai Shih-Jen, Bai Ya-Mei, Mao Wei-Chung, Tu Pei-Chi, Jeng Jia-Shyun, Li Wei-Chi
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, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan.
J Psychiatr Res. 2023 May;161:48-53. doi: 10.1016/j.jpsychires.2023.03.010. Epub 2023 Mar 6.
Whether cortical excitation and inhibition functions differ between patients with treatment-resistant depression (TRD) and strong suicidal ideation (SI) and healthy subjects and whether 0.5 mg/kg ketamine infusion can modulate cortical excitation and inhibition functions among patients with TRD-SI remain unclear.
A total of 29 patients with TRD-SI and 35 age- and sex-matched healthy controls were assessed using paired-pulse transcranial magnetic stimulation. The patients were randomly assigned to receive either a single 0.5-mg/kg ketamine or 0.045-mg/kg midazolam infusion. Depressive and suicidal symptoms were assessed at baseline and 240 min after infusion. Intracortical facilitation (ICF), short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI), all of which reflect cortical excitability and inhibition functions, were measured at the same time points.
The patients with TRD-SI had lower ICF (p < 0.001) estimates (worse cortical excitatory function) and higher SICI (p = 0.032) and LICI (p < 0.001) estimates (worse cortical inhibitory function) compared with the control group. Higher SICI estimates at baseline were associated with greater baseline suicidal symptoms. No differences were found in the SICI, ICF, and LICI estimates at 240 min after the infusion between the two groups. Low-dose ketamine did not alter the cortical excitation and inhibition functions of the patients with TRD-SI. However, decreased SICI estimates (greater cortical inhibition function) were related to the reduction of suicidal symptoms.
Dysfunction of cortical excitation and inhibition may play a crucial role in the pathomechanisms of TRD and suicidal symptoms. However, we found a lack of predictive ability of the baseline cortical excitation and inhibition parameters on the antidepressant and antisuicidal effect of low-dose ketamine infusion.
难治性抑郁症（TRD）伴强烈自杀意念（SI）的患者与健康受试者之间皮质兴奋和抑制功能是否存在差异，以及0.5mg/kg氯胺酮输注能否调节TRD-SI患者的皮质兴奋和抑制功能仍不清楚。
使用配对脉冲经颅磁刺激对29例TRD-SI患者和35例年龄及性别匹配的健康对照者进行评估。患者被随机分配接受单次0.5mg/kg氯胺酮或0.045mg/kg咪达唑仑输注。在基线和输注后240分钟评估抑郁和自杀症状。在相同时间点测量皮质内易化（ICF）、短间隔皮质内抑制（SICI）和长间隔皮质内抑制（LICI），这些均反映皮质兴奋性和抑制功能。
与对照组相比，TRD-SI患者的ICF估计值较低（p<0.001）（皮质兴奋功能较差），SICI（p=0.032）和LICI估计值较高（p<0.001）（皮质抑制功能较差）。基线时较高的SICI估计值与更严重的基线自杀症状相关。两组在输注后240分钟时的SICI、ICF和LICI估计值无差异。低剂量氯胺酮未改变TRD-SI患者的皮质兴奋和抑制功能。然而，SICI估计值降低（皮质抑制功能增强）与自杀症状减轻有关。
皮质兴奋和抑制功能障碍可能在TRD和自杀症状的发病机制中起关键作用。然而，我们发现基线皮质兴奋和抑制参数对低剂量氯胺酮输注的抗抑郁和抗自杀作用缺乏预测能力。
