Treatment response to low-dose ketamine infusion for treatment-resistant depression: A gene-based genome-wide association study
Treatment response to low-dose ketamine infusion for treatment-resistant depression: A gene-based genome-wide association study
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DOI：
10.1016/j.ygeno.2020.12.030
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发表时间：
2021-01-22
期刊：
影响因子：
4.4
通讯作者：
Su, Tung-Ping
中科院分区：
文献类型：
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作者：
Chen, Mu -Hong;Kao, Chung-Feng;Su, Tung-Ping
背景：有证据表明脑源性神经营养因子(BDNF)和谷氨酸系统在小剂量氯胺酮治疗难治性抑郁症(TRD)的抗抑郁机制中起重要作用。方法：对65例TRD患者进行684,616个单核苷酸多态性(SNPs)的基因分型。结果：与BDNF-TrkB信号转导相关的特异性SNP和全基因(即BDNF-TrkB信号通路中的rs2049048和NTRK2中的rs10217777)以及谷氨酸和GABA能系统(即，BDNF中的rs2049048和NTRK2中的rs10217777)以及谷氨酸和GABA能系统(即，GRIN2A中的rs16966731)与小剂量氯胺酮快速(240分钟内)和持续(长达2周)的抗抑郁作用以及血中氯胺酮和去甲氯胺酮水平相关。讨论：我们的研究结果证实了BDNF-TrkB信号、谷氨酸和GABA能系统在小剂量氯胺酮治疗TRD的机制中的预测作用。
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.