The relationship between of methylation brain-derived neurotrophic factor and the efficacy of ketamine in the treatment of treatment-resistant depression
10.3969/j.issn.1002-0152.2025.04.005
- VernacularTitle:脑源性神经营养因子甲基化水平与氯胺酮治疗难治性抑郁障碍疗效的关系☆
- Author:
Yuting LAN
1
;
Yanling ZHOU
;
Guanxi LIU
;
Weicheng LI
;
Xiaofeng LAN
;
Cunyou ZHAO
;
Yuping NING
Author Information
1. 南方医科大学第一临床医学院(广州 510000);广州医科大学附属脑科医院,广东省神经科学疾病研究重点实验室、神经致病基因和离子通道病教育部重点实验室
- Publication Type:Journal Article
- Keywords:
Major depressive disorder;
Treatment-resistant depression;
Ketamine;
Antidepressive therapy;
Treatment effect;
Brain-derived neurotrophic factor;
DNA methylation;
Epigenetics
- From:
Chinese Journal of Nervous and Mental Diseases
2025;51(4):232-239
- CountryChina
- Language:Chinese
-
Abstract:
Objective Based on a clinical cohort study of repeated ketamine infusions for treatment-resistant depression(TRD),this study aimed to examine differences in brain-derived neurotrophic factor(BDNF)methylation among patients with varying therapeutic responses and explore its potential role in predicting treatment efficacy.Methods A retrospective analysis was conducted on peripheral plasma BDNF levels in 83 patients with TRD before and after a 2-week course of ketamine treatment(6 injections total).The Montgomery-Asberg depression rating scale(MADRS)was used to assess treatment efficacy.BDNF methylation levels were compared between responder group and non-responder group.The effect of methylation of the target CpG site on transcriptional activity was verified by using the dual luciferase reporter gene system.Results In patients with TRD who completed six repeated ketamine infusions,the responder group showed significant improvements compared to baseline levels in both MADRS scores(25.20±7.54 vs.8.10±5.32,P<0.01)and plasma BDNF concentrations[8.74(5.26,13.46)ng/mL vs.16.59(7.41,24.46)ng/mL,P<0.01].At baseline,35 CpG sites within the BDNF gene displayed significant methylation differences between response groups(P<0.05).Two CpG sites(rs1240718851 and cg06260077)located in the BDNF promoter region demonstrated a hypermethylation-low expression correlation,and dual-luciferase reporter assays confirmed that one of these sites functionally modulates BDNF expression.Conclusions The plasma BDNF concentration in TRD patients increases with the remission of depressive symptoms.The regulation of BDNF gene expression by methylation can predict the antidepressant efficacy of repeated intravenous ketamine.
