Tu Pei-Chi, Chang Wan-Chen, Su Tung-Ping, 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, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Mol Psychiatry. 2025 Jan;30(1):61-68. doi: 10.1038/s41380-024-02640-3. Epub 2024 Jul 6.
Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is also unclear. Two resting-state functional MRIs were collected in two clinical trials of 48 patients with TRD (clinical trial 1; 32 receiving ketamine, 16 receiving a normal saline placebo) and 48 patients with TRD and strong suicidal ideation (clinical trial 2; 24 receiving ketamine, 24 receiving midazolam), respectively. All participants underwent rs-fMRI before and 3 days after infusion. Seed-based functional connectivity (FC) was analyzed in the left/right thalamus. FCs between the bilateral thalamus and right middle frontal cortex (BA46) and between the left thalamus and left anterior paracingulate gyrus (BA8) increased among patients in the ketamine group in clinical trials 1 and 2, respectively. FCs between the right thalamus and bilateral frontal pole (BA9) and between the right thalamus and left rostral paracingulate gyrus (BA10) decreased among patients in the ketamine group in clinical trials 1 and 2, respectively. However, the associations between those FC changes and clinical symptom changes did not survive statistical significance after multiple comparison corrections. Whether ketamine-related changes in thalamocortical connectivity may be associated with ketamine's antidepressant and antisuicidal effects would need further investigation. Clinical trials registration: UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000016985 and UMIN000033916.
先前的研究表明丘脑皮质功能连接障碍与难治性抑郁症（TRD）之间存在关联。单次亚麻醉剂量的氯胺酮是否会改变TRD患者的丘脑皮质连接尚不清楚。这些丘脑皮质连接的变化是否与氯胺酮治疗的抗抑郁和抗自杀作用相关也不清楚。在两项针对48例TRD患者的临床试验（临床试验1；32例接受氯胺酮治疗，16例接受生理盐水安慰剂治疗）和48例有强烈自杀意念的TRD患者（临床试验2；24例接受氯胺酮治疗，24例接受咪达唑仑治疗）中分别收集了两次静息态功能磁共振成像。所有参与者在输注前和输注后3天接受静息态功能磁共振成像检查。基于种子点的功能连接（FC）在左/右丘脑中进行分析。在临床试验1和2中，氯胺酮组患者双侧丘脑与右侧额中回（BA46）之间以及左侧丘脑与左侧前扣带回旁回（BA8）之间的FC分别增加。在临床试验1和2中，氯胺酮组患者右侧丘脑与双侧额极（BA9）之间以及右侧丘脑与左侧喙状扣带回旁回（BA10）之间的FC分别降低。然而，在进行多重比较校正后，这些FC变化与临床症状变化之间的关联未达到统计学显著性。氯胺酮相关的丘脑皮质连接变化是否可能与氯胺酮的抗抑郁和抗自杀作用相关，还需要进一步研究。临床试验注册：UMIN临床试验注册中心（UMIN-CTR）：注册号：UMIN000016985和UMIN000033916。
