BACKGROUND The symptoms of major depressive disorder (MDD) are rapidly alleviated by administration of a single dose of the glutamatergic modulator ketamine. However, few studies have investigated the potential sustained neural effects of this agent beyond immediate infusion. This study used functional magnetic resonance imaging to examine the effect of a single ketamine infusion on the resting state default mode network (DMN) at 2 and 10 days after a single ketamine infusion in unmedicated subjects with MDD as well as healthy control subjects (HCs). METHODS Data were drawn from a double-blind, placebo-controlled crossover study of 58 participants (33 with MDD and 25 HCs) who received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 separate test days spaced 2 weeks apart. Eight minutes of functional magnetic resonance imaging resting state data was acquired at baseline and at about 2 and 10 days after both infusions. The DMN was defined using seed-based correlation and was compared across groups and scans. RESULTS In subjects with MDD, connectivity between the insula and the DMN was normalized compared with HCs 2 days postketamine infusion. This change was reversed after 10 days and did not appear in either of the placebo scans. Group-specific connectivity differences in drug response were observed, most notably in the insula in subjects with MDD and in the thalamus in HCs. CONCLUSIONS Connectivity changes in the insula in subjects with MDD suggest that ketamine may normalize the interaction between the DMN and salience networks, supporting the triple network dysfunction model of MDD.

中文翻译：

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服用氯胺酮 10 天后测量重度抑郁症的默认模式连接


背景技术通过施用单剂量的谷氨酸能调节剂氯胺酮可迅速缓解重度抑郁症(MDD)的症状。然而，很少有研究调查这种药物除了立即输注之外的潜在持续神经效应。本研究使用功能磁共振成像检查单次氯胺酮输注对未接受药物治疗的 MDD 受试者以及健康对照受试者 (HC) 在单次氯胺酮输注后 2 和 10 天对静息态默认模式网络 (DMN) 的影响。方法 数据来自一项双盲、安慰剂对照交叉研究，该研究有 58 名参与者（33 名患有 MDD 和 25 名 HC），这些参与者在 2 个独立的测试日（间隔 2 天）接受静脉输注盐酸氯胺酮（0.5 mg/kg）或安慰剂。相隔几周。在基线以及两次输注后约 2 天和 10 天采集了 8 分钟的功能性磁共振成像静息态数据。 DMN 使用基于种子的相关性进行定义，并在各组和扫描之间进行比较。结果 在患有 MDD 的受试者中，与 HC 相比，氯胺酮输注后 2 天，岛叶和 DMN 之间的连接性正常化。这种变化在 10 天后逆转，并且没有出现在任何安慰剂扫描中。药物反应中观察到群体特异性连接差异，最显着的是 MDD 受试者的岛叶和 HC 的丘脑。结论 MDD 受试者岛叶的连接性变化表明，氯胺酮可能使 DMN 和显着网络之间的相互作用正常化，支持 MDD 的三重网络功能障碍模型。