Tsai Shih-Jen, Hong Chen-Jee, Liou Ying-Jay, Chen Tai-Jui, Chen Mao-Liang, Hou Sheue-Jane, Yen Feng-Chang, Yu Younger W-Y
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
Psychiatry Res. 2009 Sep 30;169(2):113-7. doi: 10.1016/j.psychres.2008.06.028. Epub 2009 Aug 22.
Vascular endothelial growth factor (VEGF) has been implicated in neurotrophy and neurogenesis, which play a pivotal role in brain development and may be involved in antidepressant therapeutic mechanisms. Recent animal studies demonstrate that VEGF levels are increased by several antidepressants, including selective serotonin reuptake inhibitors, and that VEGF signalling is required for antidepressant-induced behavioural response. We hypothesized that common genetic variants in the VEGF gene (official gene name: VEGFA) may be associated with the therapeutic response to antidepressants in major depressive disorders (MDD). Seven VEGFA polymorphisms were genotyped in 351 patients with MDD who were treated with selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressants and who were were studied in a therapeutic evaluation for at least 4 weeks. Of the 351 patients, 158 completed an 8-week therapeutic evaluation. No significant association with either 4-week or 8-week antidepressant therapeutic effect was shown in the alleles and genotypes of single loci, or haplotypes from two blocks constructed from these polymorphisms. Our findings suggested that VEGFA genetic variants do not play a major role in the response to selective serotonin reuptake inhibitors.
血管内皮生长因子(VEGF)与神经营养和神经发生有关,这在大脑发育中起关键作用,并且可能参与抗抑郁治疗机制。最近的动物研究表明,包括选择性5-羟色胺再摄取抑制剂在内的几种抗抑郁药可提高VEGF水平,且抗抑郁药诱导的行为反应需要VEGF信号传导。我们假设血管内皮生长因子基因(官方基因名称:VEGFA)中的常见基因变异可能与重度抑郁症(MDD)患者对抗抑郁药的治疗反应有关。对351例接受选择性5-羟色胺再摄取抑制剂(氟西汀或西酞普兰)抗抑郁药治疗且接受了至少4周治疗评估的MDD患者进行了7种VEGFA多态性的基因分型。在这351例患者中,158例完成了为期8周的治疗评估。这些多态性构建的两个区域的单基因座等位基因和基因型或单倍型与4周或8周抗抑郁治疗效果均无显著关联。我们的研究结果表明,VEGFA基因变异在对选择性5-羟色胺再摄取抑制剂的反应中不发挥主要作用。