脑源性神经营养因子 Val66Met 多态性对不同形式的前额叶脑刺激单药治疗抗抑郁疗效的预测作用：一项随机、双盲、假刺激对照研究。
Predictive roles of brain-derived neurotrophic factor Val66Met polymorphism on antidepressant efficacy of different forms of prefrontal brain stimulation monotherapy: A randomized, double-blind, sham-controlled study.
机构信息
Institute of Brain Science, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, No.201, Sec.2, Shih-Pai Road, Beitou district, Taipei 112, Taiwan; Division of Psychiatry, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department and Institute of Physiology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
出版信息
J Affect Disord. 2022 Jan 15;297:353-359. doi: 10.1016/j.jad.2021.10.077. Epub 2021 Oct 29.
BACKGROUND
Although repetitive transcranial magnetic stimulation (rTMS) and prolonged intermittent theta-burst stimulation (piTBS) can induce changes in synaptic plasticity, the influence of brain-derived neurotrophic factor (BDNF) genotypes on their antidepressant effects remain unknown. Hence, we investigated the BDNF polymorphism contribution to the antidepressant effect of different forms left-sided prefrontal stimulations in a randomized, sham-controlled study METHODS: Seventy-five patients with medication-resistant depression were randomly assigned into three monotherapy groups: piTBS, high-frequency(HF) rTMS, or sham. The acute treatment period was two weeks. 17-item Hamilton Depression Rating scale (HDRS-17) were applied at baseline, week-1, and week-2. The primary outcome was percentage changes of HDRS-17 (%HDRS-17 changes) analyzed by generalized estimating equation (GEE) model.
RESULTS
The GEE analysis revealed a significant interaction between group, time, and BDNF genotypes effects on %HDRS-17 changes over time. In patients carrying Val homozygotes, piTBS and HF-rTMS both exhibited significantly greater %HDRS reduction than sham at week-2. In Met carriers, only piTBS showed better efficacy than sham at week-2 (piTBS vs. sham, -41.1% vs.-18.9%, p=0.004). Regarding the influence of different BDNF genotypes on antidepressant efficacy in each intervention, only HF-rTMS exhibited significantly different degrees of %HDRS-17 changes between Val homozygotes and Met carriers (-68.5% vs. -26.4%, p=0.012, respectively), but piTBS delivered the consistent efficacy regardless of the BDNF polymorphism.
CONCLUSIONS
This is the first study to confirm the different impacts of BDNF genotypes on the effect of different left-sided prefrontal brain stimulation. BDNF Val66Met polymorphism may play a role in the antidepressant response of piTBS and HF-rTMS. (Trial Registration Number UMIN-CTR:UMIN000020892: Registration date: Feb.4, 2016).
背景
尽管重复经颅磁刺激（rTMS）和延长的间歇性 theta 爆发刺激（piTBS）可以诱导突触可塑性的变化，但脑源性神经营养因子（BDNF）基因型对其抗抑郁作用的影响尚不清楚。因此，我们在一项随机、假对照研究中，研究了 BDNF 多态性对不同形式左侧前额叶刺激的抗抑郁作用的贡献。
方法
75 名药物难治性抑郁症患者被随机分配到三个单药治疗组：piTBS、高频（HF）rTMS 或假刺激。急性治疗期为两周。基线、第 1 周和第 2 周应用 17 项汉密尔顿抑郁量表（HDRS-17）。采用广义估计方程（GEE）模型分析主要结局指标为 HDRS-17 评分的百分比变化（%HDRS-17 变化）。
结果
GEE 分析显示，组间、时间和 BDNF 基因型对 %HDRS-17 变化的交互作用有显著影响。在携带 Val 纯合子的患者中，piTBS 和 HF-rTMS 在第 2 周时均较假刺激显示出更显著的 %HDRS 降低。在 Met 携带者中，只有 piTBS 在第 2 周时比假刺激显示出更好的疗效（piTBS 与假刺激相比，-41.1%与-18.9%，p=0.004）。关于不同 BDNF 基因型对每种干预措施抗抑郁疗效的影响，只有 HF-rTMS 在 Val 纯合子和 Met 携带者之间显示出 %HDRS-17 变化的显著差异（-68.5%与-26.4%，p=0.012），而 piTBS 则表现出一致的疗效，而与 BDNF 多态性无关。
结论
这是第一项证实 BDNF 基因型对不同左侧前额叶脑刺激效果的不同影响的研究。BDNF Val66Met 多态性可能在 piTBS 和 HF-rTMS 的抗抑郁反应中起作用。（临床试验注册号 UMIN-CTR：UMIN000020892：注册日期：2016 年 2 月 4 日）。
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