Institute of Health And Wellbeing, University of Glasgow, Glasgow, Scotland.
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2018 Sep 21;13(9):e0203896. doi: 10.1371/journal.pone.0203896. eCollection 2018.
There are currently no reliable approaches for correctly identifying which patients with major depressive disorder (MDD) will respond well to antidepressant therapy. However, recent genetic advances suggest that Polygenic Risk Scores (PRS) could allow MDD patients to be stratified for antidepressant response. We used PRS for MDD and PRS for neuroticism as putative predictors of antidepressant response within three treatment cohorts: The Genome-based Therapeutic Drugs for Depression (GENDEP) cohort, and 2 sub-cohorts from the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study PRGN-AMPS (total patient number = 760). Results across cohorts were combined via meta-analysis within a random effects model. Overall, PRS for MDD and neuroticism did not significantly predict antidepressant response but there was a consistent direction of effect, whereby greater genetic loading for both MDD (best MDD result, p < 5*10-5 MDD-PRS at 4 weeks, β = -0.019, S.E = 0.008, p = 0.01) and neuroticism (best neuroticism result, p < 0.1 neuroticism-PRS at 8 weeks, β = -0.017, S.E = 0.008, p = 0.03) were associated with less favourable response. We conclude that the PRS approach may offer some promise for treatment stratification in MDD and should now be assessed within larger clinical cohorts.
目前，尚无可靠的方法可以正确识别哪些患有重度抑郁症（MDD）的患者对抗抑郁治疗有良好的反应。但是，最近的遗传进展表明，多基因风险评分（PRS）可以使 MDD 患者在抗抑郁反应方面分层。我们使用 MDD 的 PRS 和神经质的 PRS 作为抗抑郁反应的潜在预测因子，在三个治疗队列中进行了研究：基于基因组的抗抑郁药物治疗（GENDEP）队列，以及 Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study PRGN-AMPS 的 2 个亚队列（总患者数=760）。通过随机效应模型在荟萃分析中合并了来自各个队列的结果。总体而言，MDD 和神经质的 PRS 并未显著预测抗抑郁反应，但存在一致的效应方向，即 MDD（最佳 MDD 结果，p < 5*10-5 MDD-PRS 在 4 周时，β= -0.019，S.E= 0.008，p = 0.01）和神经质（最佳神经质结果，p < 0.1 神经质-PRS 在 8 周时，β= -0.017，S.E= 0.008，p = 0.03）的遗传负荷更高与反应较差相关。我们的结论是，PRS 方法可能为 MDD 的治疗分层提供了一些希望，现在应该在更大的临床队列中进行评估。
