Shiroma Paulo R, Drews Maureen S, Geske Jennifer R, Mrazek David A
Geriatric Psychiatry Clinic, Mental Health Service Line, Minneapolis VA Medical Center, University of Minnesota Medical School, Minneapolis, MN.
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.
Am J Geriatr Psychiatry. 2014 Nov;22(11):1140-8. doi: 10.1016/j.jagp.2013.02.012. Epub 2013 Aug 20.
Age at onset of first major depressive episode (MDE) does not necessarily translate into different treatment outcomes to antidepressants in late-life depression. The influence of genetic variants may affect this relationship.
Post hoc data set analysis of the association between variants in the promoter region (indel, rs25531) and within intron 2 (Stin2 VNTR) of the SCL6A4 gene and treatment outcomes among older participants in the first treatment arm of the Sequenced Treatment Alternatives to Relieve Depression trial (STAR*D).
Participants were enrolled from 23 psychiatric and 18 primary care settings.
Two hundred twenty-one, white non-Hispanic subjects, aged 60 to 75 years, with 16-item Quick Inventory of Depressive Symptomatology-Clinician Rating (QIDS-CR16) initial score ≥10, and who remained in the study for at least 6 weeks, were genotyped.
Citalopram treatment for up to 14 weeks.
Main outcome was remission rate defined as a score of ≤5 on the QIDS-CR16. Response was a secondary outcome defined as a reduction of ≥50% of baseline QIDS-CR16.
Polymorphism in the indel promoter region was associated with remission among subjects whose first lifetime episode of major depression occurred later than age 55. In this group, subjects with L/L genotype had significantly higher remission (80% versus 43%) compared to those subjects with any other indel promoter genotype. Multivariate analysis demonstrated that the genetic effect of the indel promoter region on remission increases along with age at onset of MDE.
Variants in the indel promoter region of the SLC6A4 gene have a more robust effect to antidepressant outcome among older subjects who experienced their first MDE at a later age. The mechanism of action of these variants remains to be determined.
首次重度抑郁发作（MDE）的发病年龄并不一定会转化为老年抑郁症患者对抗抑郁药的不同治疗结果。基因变异的影响可能会影响这种关系。
对缓解抑郁试验（STAR*D）首个治疗组中年龄较大参与者的SCL6A4基因启动子区域（插入缺失，rs25531）和内含子2（Stin2可变数目串联重复序列）中的变异与治疗结果之间的关联进行事后数据集分析。
参与者来自23个精神科和18个初级保健机构。
221名60至75岁的非西班牙裔白人受试者，16项抑郁症状快速自评量表-临床医生评定版（QIDS-CR16）初始评分≥10，且在研究中至少停留6周，进行了基因分型。
西酞普兰治疗长达14周。
主要结局是缓解率，定义为QIDS-CR16评分≤5。反应是次要结局，定义为基线QIDS-CR16降低≥50%。
插入缺失启动子区域的多态性与首次重度抑郁发作发生在55岁以后的受试者的缓解有关。在这组受试者中，L/L基因型的受试者缓解率（80%对43%）显著高于其他任何插入缺失启动子基因型的受试者。多变量分析表明，插入缺失启动子区域对缓解的遗传效应随着MDE发病年龄的增加而增加。
SLC6A4基因插入缺失启动子区域的变异对首次MDE发病较晚的老年受试者的抗抑郁结果有更强的影响。这些变异的作用机制仍有待确定。
