Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
Pharmacogenomics J. 2011 Apr;11(2):146-54. doi: 10.1038/tpj.2010.12. Epub 2010 Mar 2.
Although not observed in younger adult cohorts, in older individuals the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with major depressive disorder (MDD) risk. It is further associated with subjective social support and magnetic resonance imaging (MRI) hyperintense lesions, clinical features independently related to MDD. We examined the relationship between this polymorphism and antidepressant remission rates in an elderly sample with MDD, while also testing for mediation effects of social support and hyperintensities. A total of 229 elderly Caucasian subjects with MDD completed baseline assessments, 1.5 T MRI, and BDNF genotyping. They received antidepressant medication under a structured treatment algorithm and were evaluated for remission at 3 and 6 months. At the 3-month evaluation, BDNF Val66Met genotype was not associated with remission (Wald's χ²=2.51, P=0.1131). When not controlling for multiple comparisons, Met66 allele carriers were more likely to be remitted at 6 months (χ²=4.32, P=0.0377) with an odds ratio of 1.82 (95% CI: 1.04, 3.22). This effect persisted after controlling for lesion volume and social support, neither of which mediated this relationship. Thus in this exploratory analysis, the Met66 allele may be associated with increased odds of remission in older subjects, but also with increased time to remission as there was no 3-month effect.
尽管在年轻的成年人群中没有观察到,但在老年人中,脑源性神经营养因子(BDNF)Val66Met 多态性与重度抑郁症(MDD)风险相关。它还与主观社会支持和磁共振成像(MRI)高信号病变相关,这些病变是与 MDD 独立相关的临床特征。我们在 MDD 的老年患者样本中研究了这种多态性与抗抑郁药缓解率之间的关系,同时还测试了社会支持和高信号病变的中介作用。共有 229 名患有 MDD 的老年白种人受试者完成了基线评估、1.5T MRI 和 BDNF 基因分型。他们根据结构化治疗算法接受抗抑郁药物治疗,并在 3 个月和 6 个月时评估缓解情况。在 3 个月的评估中,BDNF Val66Met 基因型与缓解无关(Wald's χ²=2.51,P=0.1131)。当不控制多次比较时,Met66 等位基因携带者在 6 个月时更有可能缓解(χ²=4.32,P=0.0377),优势比为 1.82(95%CI:1.04,3.22)。在控制病变体积和社会支持后,这种效应仍然存在,而这两者都没有介导这种关系。因此,在这项探索性分析中,Met66 等位基因可能与老年患者缓解的几率增加有关,但也与缓解时间的增加有关,因为在 3 个月时没有效果。