Monoamine neurotransmitter-related gene-based genome-wide association study of low-dose ketamine in patients with treatment-resistant depression.

IF 4.5 3区 医学 Q1 CLINICAL NEUROLOGY
Chung-Feng Kao, Shih-Jen Tsai, Tung-Ping Su, Cheng-Ta Li, Wei-Chen Lin, Chen-Jee Hong, Ya-Mei Bai, Pei-Chi Tu, Mu-Hong Chen
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引用次数: 0

Abstract

Background: Low-dose ketamine is an N-methyl-D-aspartate receptor antagonist that exerts an antidepressant effect on patients with treatment-resistant depression (TRD). This antidepressant effect may extend beyond the glutamatergic hypothesis. Nevertheless, the roles of genes encoding other monoamine neurotransmitters (i.e., serotonin and dopamine) in the neuromechanism of low-dose ketamine remain unknown.

Methods: In this clinical trial, which involved 65 patients with TRD, 21 patients received 0.5 mg/kg ketamine, 20 received 0.2 mg/kg ketamine, and 24 received normal saline. All patients were genotyped for 684,616 single-nucleotide polymorphisms (SNPs). A total of 50 monoamine neurotransmitter-related candidate genes, including HTR2A and HTR2C from the serotoninergic system, CHRM4 and CHRNB1 from the cholinergic system, and DRD2 from the dopaminergic system, were selected to conduct a gene-based genome-wide association study of the antidepressant effects of ketamine.

Results: Gene-set enrichment analysis revealed that the pathway underlying neuroactive ligand-receptor interaction (KEGG) played a pivotal role in the biomechanisms underlying ketamine's antidepressant effect. Specifically, the genes and SNPs related to the cholinergic system (e.g., rs2644247 in CHRM5), μ1 opioid receptor (e.g., rs2473546 in OPRM1), dopaminergic system (e.g., rs2617577 in SLC6A3), serotonergic system (HTR2A), cannabinoid receptor (CNR2), and σ1 receptor (SIGMAR1) were associated with the antidepressant effect of low-dose ketamine.

Discussion: Low-dose ketamine has an antidepressant effect, which may be associated with multiple monoamine neurotransmitter systems and the σ1 receptor.

低剂量氯胺酮治疗难治性抑郁症患者的单胺类神经递质相关基因全基因组关联研究
背景:低剂量氯胺酮是一种n -甲基-d -天冬氨酸受体拮抗剂,对难治性抑郁症(TRD)患者具有抗抑郁作用。这种抗抑郁作用可能超出了谷氨酸能假说。然而,编码其他单胺类神经递质(即血清素和多巴胺)的基因在低剂量氯胺酮的神经机制中的作用仍然未知。方法:65例TRD患者,21例给予0.5 mg/kg氯胺酮治疗,20例给予0.2 mg/kg氯胺酮治疗,24例给予生理盐水治疗。所有患者均为684,616个单核苷酸多态性(snp)进行基因分型。共选择50个单胺类神经递质相关候选基因,包括5 -羟色胺系统的HTR2A和HTR2C,胆碱系统的CHRM4和CHRNB1,以及多巴胺能系统的DRD2,对氯胺酮的抗抑郁作用进行基于基因的全基因组关联研究。结果:基因集富集分析显示,神经活性配体-受体相互作用(KEGG)通路在氯胺酮抗抑郁作用的生物机制中起关键作用。其中,胆碱能系统(如CHRM5中的rs2644247)、μ1阿片受体(如OPRM1中的rs2473546)、多巴胺能系统(如SLC6A3中的rs2617577)、血清素能系统(HTR2A)、大麻素受体(CNR2)和σ1受体(SIGMAR1)相关的基因和snp与低剂量氯胺酮的抗抑郁作用有关。讨论:小剂量氯胺酮具有抗抑郁作用,这可能与多单胺类神经递质系统和σ1受体有关。
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来源期刊
Journal of Psychopharmacology
Journal of Psychopharmacology 医学-精神病学
CiteScore
8.60
自引率
4.90%
发文量
126
审稿时长
3-8 weeks
期刊介绍: The Journal of Psychopharmacology is a fully peer-reviewed, international journal that publishes original research and review articles on preclinical and clinical aspects of psychopharmacology. The journal provides an essential forum for researchers and practicing clinicians on the effects of drugs on animal and human behavior, and the mechanisms underlying these effects. The Journal of Psychopharmacology is truly international in scope and readership.
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