Backgrounds

Evidence suggested the crucial roles of brain-derived neurotrophic factor (BDNF) and glutamate system functioning in the antidepressant mechanisms of low-dose ketamine infusion in treatment-resistant depression (TRD).

Methods

65 patients with TRD were genotyped for 684,616 single nucleotide polymorphisms (SNPs). Twelve ketamine-related genes were selected for the gene-based genome-wide association study on the antidepressant effect of ketamine infusion and the resulting serum ketamine and norketamine levels.

Results

Specific SNPs and whole genes involved in BDNF–TrkB signaling (i.e., rs2049048 in BDNF and rs10217777 in NTRK2) and the glutamatergic and GABAergic systems (i.e., rs16966731 in GRIN2A) were associated with the rapid (within 240 min) and persistent (up to 2 weeks) antidepressant effect of low-dose ketamine infusion and with serum ketamine and norketamine levels.

Discussion

Our findings confirmed the predictive roles of BDNF–TrkB signaling and glutamatergic and GABAergic systems in the underlying mechanisms of low-dose ketamine infusion for TRD treatment.

中文翻译：

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低剂量氯胺酮输注治疗难治性抑郁症的治疗反应：基于基因的全基因组关联研究

背景

证据表明脑源性神经营养因子 (BDNF) 和谷氨酸系统在难治性抑郁症 (TRD) 中低剂量氯胺酮输注的抗抑郁机制中发挥重要作用。

方法

对 65 名 TRD 患者进行了 684,616 个单核苷酸多态性 (SNP) 的基因分型。选择 12 个氯胺酮相关基因用于基于基因的全基因组关联研究，研究氯胺酮输注的抗抑郁作用以及由此产生的血清氯胺酮和去甲氯胺酮水平。

结果

参与 BDNF-TrkB 信号传导的特定 SNP 和全基因（即BDNF中的 rs2049048和 NTRK2 中的rs10217777）以及谷氨酸能和 GABA 能系统（即 GRIN2A 中的rs16966731）与快速（240 分钟内）和持续（最多2周）低剂量氯胺酮输注和血清氯胺酮和去甲氯胺酮水平的抗抑郁作用。

讨论

我们的研究结果证实了 BDNF-TrkB 信号传导和谷氨酸能和 GABA 能系统在低剂量氯胺酮输注治疗 TRD 的潜在机制中的预测作用。