Elsevier

Genomics

Volume 113, Issue 2, March 2021, Pages 507-514
Genomics

Original Article
Treatment response to low-dose ketamine infusion for treatment-resistant depression: A gene-based genome-wide association study

https://doi.org/10.1016/j.ygeno.2020.12.030Get rights and content
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Highlights

  • The specific genes involving BDNF–TrkB signaling and glutamatergic system may predict the rapid antidepressant effect of ketamine.

  • Several SNPs in NTRK2, GRIN2A, and GRIN2B are related to the resulting serum levels of ketamine and norketamine after infusion.

  • Those genes may be involved in NMDAR blockade, GABA and glutamate nerve terminals, and postsynaptic dendritic spines.

Abstract

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.

Keywords

Ketamine
Treatment response
Genome-wide association studies
Brain-derived neurotrophic factor

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