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

This article focuses on a gene-based genome-wide association study (GWAS) investigating the roles of monoamine neurotransmitter-related genes and single-nucleotide polymorphisms (SNPs) in the antidepressant effects of low-dose ketamine in patients with treatment-resistant depression (TRD). In a clinical trial involving 65 Taiwanese patients with TRD, genetic variants in cholinergic (e.g., CHRM5), serotonergic (e.g., HTR2A, HTR2B), dopaminergic (e.g., SLC6A3, DRD2), opioidergic (e.g., OPRM1), cannabinoid (CNR2), and σ1 receptor (SIGMAR1) genes were associated with ketamine's rapid and sustained antidepressant response. Pathway enrichment analysis highlighted the neuroactive ligand–receptor interaction pathway as central to ketamine's mechanism of action, suggesting that its antidepressant effects involve multiple neurotransmitter systems beyond the glutamatergic hypothesis. The study acknowledges limitations including small sample size and population specificity, indicating the need for further research to generalize these findings.