Department of Agronomy, National Chung Hsing University, Taichung, Taiwan.
Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan.
Sci Rep. 2018 May 3;8(1):6983. doi: 10.1038/s41598-018-25529-y.
It is well established that brain-derived neurotrophic factor (BDNF) signaling pathway plays a key role in the pathophysiology of major depressive disorder (MDD) and in therapeutic mechanisms of antidepressants. We aim to identify genetic vairiants related to MDD susceptibility and antidepressant therapeutic response by using gene-based association analysis with genes related to the neurotrophic pathway. The present study investigated the role of genetic variants in the 10 neurotrophic-related genes (BDNF, NGFR, NTRK2, MTOR, VEGFA, S100A10, SERPINE1, ARHGAP33, GSK3B, CREB1) in MDD susceptibility through a case-control (455 MDD patients and 2,998 healthy controls) study and in antidepressant efficacy (n = 455). Measures of antidepressant therapeutic efficacy were evaluated using the 21-item Hamilton Rating Scale for Depression. Our single-marker and gene-based analyses with ten genes related to the neurotrophic pathway identified 6 polymorphisms that reached a significant level (p-value < 5.0 × 10) in both meta- and mega-analyses in antidepressant therapeutic response. One polymorphism was mapped to BDNF and 5 other polymorphisms were mapped to VEGFA. For case-control association study, we found that all of these reported polymorphisms and genes did not reach a suggestive level. The present study supported a role of BDNF and VEGFA variants in MDD therapeutic response.
已有充分证据表明，脑源性神经营养因子（BDNF）信号通路在重度抑郁症（MDD）的病理生理学和抗抑郁药的治疗机制中起着关键作用。我们旨在通过基于基因的关联分析，寻找与神经营养途径相关的基因，来确定与 MDD 易感性和抗抑郁药治疗反应相关的遗传变异。本研究通过病例对照（455 名 MDD 患者和 2998 名健康对照）研究和抗抑郁疗效（n=455），调查了 10 个神经营养相关基因（BDNF、NGFR、NTRK2、MTOR、VEGFA、S100A10、SERPINE1、ARHGAP33、GSK3B、CREB1）中的遗传变异与 MDD 易感性的关系。抗抑郁疗效的衡量标准是使用 21 项汉密尔顿抑郁量表（Hamilton Rating Scale for Depression）进行评估。我们对与神经营养途径相关的十个基因进行了单标记和基于基因的分析，在抗抑郁治疗反应的元分析和 mega 分析中，有 6 个多态性达到了显著水平（p 值<5.0×10）。其中一个多态性位于 BDNF 上，另外 5 个多态性位于 VEGFA 上。对于病例对照关联研究，我们发现报告的所有这些多态性和基因都没有达到提示水平。本研究支持 BDNF 和 VEGFA 变异在 MDD 治疗反应中的作用。
