Lekman Magnus, Laje Gonzalo, Charney Dennis, Rush A John, Wilson Alexander F, Sorant Alexa J M, Lipsky Robert, Wisniewski Stephen R, Manji Husseini, McMahon Francis J, Paddock Silvia
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Biol Psychiatry. 2008 Jun 15;63(12):1103-10. doi: 10.1016/j.biopsych.2007.10.026. Epub 2008 Jan 11.
In a recent study of several antidepressant drugs in hospitalized, non-Hispanic White patients, Binder et al. reported association of markers located within the FKBP5 gene with treatment response after 2 and 5 weeks. Individuals homozygous for the TT-genotype at one of the markers (rs1360780) reported more depressive episodes and responded better to antidepressant treatment. There was no association between markers in FKBP5 and disease. The present study aimed at studying the associated FKBP5 markers in the ethnically diverse Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample of non-hospitalized patients treated with citalopram.
We used clinical data and DNA samples from 1809 outpatients with non-psychotic major depressive disorder (DSM-IV criteria), who received up to 14 weeks of citalopram. A subset of 1523 patients of White non-Hispanic or Black race was matched with 739 control subjects for a case-control analysis. The markers rs1360780 and rs4713916 were genotyped on the Illumina platform. TaqMan-assay was used for marker rs3800373.
In the case-control analysis, marker rs1360780 was significantly associated with disease status in the White non-Hispanic sample after correction for multiple testing. A significant association was also found between rs4713916 and remission. Markers rs1360780 and rs4713916 were in strong linkage disequilibrium in the White non-Hispanic but not in the Black population. There was no significant difference in the number of previous episodes of depression between genotypes at any of the three markers.
These results indicate that FKBP5 is an important target for further studies of depression and treatment response.
在最近一项针对住院的非西班牙裔白人患者的几种抗抑郁药物的研究中,Binder等人报告称,位于FKBP5基因内的标记物与2周和5周后的治疗反应相关。在其中一个标记物(rs1360780)处为TT基因型纯合子的个体报告有更多抑郁发作,且对抗抑郁治疗反应更好。FKBP5中的标记物与疾病之间无关联。本研究旨在研究在接受西酞普兰治疗的非住院患者的种族多样化的缓解抑郁序列治疗替代方案(STAR*D)样本中与FKBP5相关的标记物。
我们使用了1809名患有非精神病性重度抑郁症(符合《精神疾病诊断与统计手册》第四版标准)的门诊患者的临床数据和DNA样本,这些患者接受了长达14周的西酞普兰治疗。对1523名非西班牙裔白人或黑人患者的子集与739名对照受试者进行匹配,以进行病例对照分析。在Illumina平台上对标记物rs1360780和rs4713916进行基因分型。使用TaqMan分析对标记物rs3800373进行检测。
在病例对照分析中,经过多重检验校正后,标记物rs1360780在非西班牙裔白人样本中与疾病状态显著相关。在rs4713916与缓解之间也发现了显著关联。标记物rs1360780和rs4713916在非西班牙裔白人中处于强连锁不平衡状态,但在黑人人群中并非如此。在这三个标记物的任何一个基因型之间,既往抑郁发作次数均无显著差异。
这些结果表明,FKBP5是抑郁症及治疗反应进一步研究的重要靶点。