Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Eur Neuropsychopharmacol. 2022 Feb;55:86-95. doi: 10.1016/j.euroneuro.2021.11.005. Epub 2021 Nov 26.
About two-thirds of patients with major depressive disorder (MDD) fail to achieve symptom remission after the initial antidepressant treatment. Despite a role of genetic factors was proven, the specific underpinnings are not fully understood yet. Polygenic risk scores (PRSs), which summarise the additive effect of multiple risk variants across the genome, might provide insights into the underlying genetics. This study aims to investigate the possible association of PRSs for bipolar disorder, MDD, neuroticism, and schizophrenia (SCZ) with antidepressant non-response or non-remission in patients with MDD. PRSs were calculated at eight genome-wide P-thresholds based on publicly available summary statistics of the largest genome-wide association studies. Logistic regressions were performed between PRSs and non-response or non-remission in six European clinical samples, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, including up to 3,637 individuals. Bonferroni correction was applied. In the meta-analysis, no result was significant after Bonferroni correction. The top result was found for MDD-PRS and non-remission (p = 0.004), with patients in the highest vs. lowest PRS quintile being more likely not to achieve remission (OR=1.5, 95% CI=1.11-1.98, p = 0.007). Nominal associations were also found between MDD-PRS and non-response (p = 0.013), as well as between SCZ-PRS and non-remission (p = 0.035). Although PRSs are still not able to predict non-response or non-remission, our results are in line with previous works; methodological improvements in PRSs calculation may improve their predictive performance and have a meaningful role in precision psychiatry.
大约三分之二的重度抑郁症（MDD）患者在初始抗抑郁治疗后未能达到症状缓解。尽管遗传因素的作用已得到证实，但具体的基础仍不完全清楚。多基因风险评分（PRSs），可以概括基因组中多个风险变异的累加效应，可能为潜在遗传学提供见解。本研究旨在调查双相情感障碍、MDD、神经质和精神分裂症（SCZ）的 PRS 与 MDD 患者抗抑郁药无反应或无缓解之间的可能关联。基于最大的全基因组关联研究的公开汇总统计数据，在八个全基因组 P 阈值下计算 PRS。在六个欧洲临床样本中，使用逻辑回归在调整年龄、性别、基线症状严重程度、招募地点和人群分层后，将 PRS 与无反应或无缓解进行比较。在样本之间进行荟萃分析，包括多达 3637 个人。进行了 Bonferroni 校正。荟萃分析中，经 Bonferroni 校正后没有结果具有统计学意义。在 MDD-PRS 和无缓解方面发现了最高的结果（p=0.004），最高与最低 PRS 五分位数的患者更不可能达到缓解（OR=1.5，95%CI=1.11-1.98，p=0.007）。在 MDD-PRS 与无反应（p=0.013）以及 SCZ-PRS 与无缓解（p=0.035）之间也发现了名义关联。尽管 PRS 目前仍无法预测无反应或无缓解，但我们的结果与以前的研究一致；PRS 计算方法的改进可能会提高其预测性能，并在精准精神病学中具有重要作用。
