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连接失调与难治性抑郁症（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。丘脑皮质连接的这些变化是否与氯胺酮治疗的抗抑郁和抗自杀作用有关也尚不清楚。在两项临床试验中收集了两张静息态功能 MRI 图像，其中包括 48 名 TRD 患者（临床试验 1；32 名接受氯胺酮治疗，16 名接受生理盐水安慰剂）和 48 名 TRD 且有强烈自杀意念的患者（临床试验 2；24 名接受氯胺酮治疗） ，24 人分别接受咪达唑仑）。所有参与者在输注前和输注后 3 天均接受了 rs-fMRI。对左/右丘脑基于种子的功能连接（FC）进行了分析。在临床试验 1 和 2 中，氯胺酮组患者的双侧丘脑和右额中皮质 (BA46) 之间以及左侧丘脑和左前副扣带回 (BA8) 之间的 FC 分别增加。在临床试验 1 和 2 中，氯胺酮组患者的右侧丘脑和双侧额极 (BA9) 之间以及右侧丘脑和左侧头侧扣带回 (BA10) 之间的 FC 分别降低。然而，经过多重比较校正后，这些 FC 变化与临床症状变化之间的关联并不具有统计学意义。氯胺酮相关的丘脑皮质连接变化是否与氯胺酮的抗抑郁和抗自杀作用有关，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。