Zhou Xiangjun, Qu Yucai, Shi Lingyi, Du Zhiqiang, Zhou Qin, Zhou Zhenhe, Jiang Ying, Zhu Haohao
Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, 214151, Jiangsu, China.
Eur Arch Psychiatry Clin Neurosci. 2025 Sep 16. doi: 10.1007/s00406-025-02117-6.
To explore the causal relationship between 2,821 plasma protein level ratios and antidepressant treatment response to uncover the potential molecular mechanisms.
We utilized the protein level ratio dataset from the UK Biobank Pharma Proteomics Project (UKB PPP) and the antidepressant treatment dataset from the Psychiatric Genomics Consortium. We employed Mendelian Randomization (MR) analysis to explore the causal relationships between 2,821 protein level ratios and antidepressant treatment. Additionally, we conducted GO/KEGG analysis to uncover associated biological processes, cellular components, molecular functions, and signaling pathways.
We found that the protein level ratio of ANXA11/ANXA3 was significantly positively associated with the positive effects of antidepressant treatment(IVW method(FEM): OR = 1.537, 95%CI = 1.263-1.869, p = 1.730E-05, pFDR = 0.049), suggesting its potential as a biomarker for predicting antidepressant efficacy. Moreover, the GO/KEGG analysis provided new insights into the genetic architecture and molecular mechanisms underlying antidepressant efficacy.
Our results highlight the significance of protein level ratios in the pathophysiological processes of depression and offer novel strategies for the development of personalized treatment approaches. Future studies are warranted to further validate these findings and explore their clinical implications.
探讨2821种血浆蛋白水平比值与抗抑郁治疗反应之间的因果关系,以揭示潜在的分子机制。
我们利用了英国生物银行药物蛋白质组学项目(UKB PPP)的蛋白质水平比值数据集和精神基因组学联盟的抗抑郁治疗数据集。我们采用孟德尔随机化(MR)分析来探讨2821种蛋白质水平比值与抗抑郁治疗之间的因果关系。此外,我们进行了GO/KEGG分析,以揭示相关的生物学过程、细胞成分、分子功能和信号通路。
我们发现ANXA11/ANXA3的蛋白质水平比值与抗抑郁治疗的积极效果显著正相关(逆方差加权法(FEM):OR = 1.537,95%CI = 1.263 - 1.869,p = 1.730E - 05,pFDR = 0.049),表明其作为预测抗抑郁疗效生物标志物的潜力。此外,GO/KEGG分析为抗抑郁疗效的遗传结构和分子机制提供了新的见解。
我们的结果突出了蛋白质水平比值在抑郁症病理生理过程中的重要性,并为个性化治疗方法的开发提供了新策略。未来的研究有必要进一步验证这些发现并探索其临床意义。