Engelke Rudolf, Ouanes Sami, Ghuloum Suhaila, Chamali Rifka, Kiwan Nancy, Sarwath Hina, Schmidt Frank, Suhre Karsten, Al-Amin Hassen
Proteomics Core, Research Department, Weill Cornell Medicine in Qatar, Doha, Qatar.
Psychiatry Department, Hamad Medical Corporation, Doha, Qatar.
Front Psychiatry. 2022 Apr 25;13:809071. doi: 10.3389/fpsyt.2022.809071. eCollection 2022.
Schizophrenia (SZ) and bipolar disorder (BD) share many features: overlap in mood and psychotic symptoms, common genetic predisposition, treatment with antipsychotics (APs), and similar metabolic comorbidities. The pathophysiology of both is still not well defined, and no biomarkers can be used clinically for diagnosis and management. This study aimed to assess the plasma proteomics profile of patients with SZ and BD maintained on APs compared to those who had been off APs for 6 months and to healthy controls (HCs).
We analyzed the data using functional enrichment, random forest modeling to identify potential biomarkers, and multivariate regression for the associations with metabolic abnormalities.
We identified several proteins known to play roles in the differentiation of the nervous system like NTRK2, CNTN1, ROBO2, and PLXNC1, which were downregulated in AP-free SZ and BD patients but were "normalized" in those on APs. Other proteins (like NCAM1 and TNFRSF17) were "normal" in AP-free patients but downregulated in patients on APs, suggesting that these changes are related to medication's effects. We found significant enrichment of proteins involved in neuronal plasticity, mainly in SZ patients on APs. Most of the proteins associated with metabolic abnormalities were more related to APs use than having SZ or BD. The biomarkers identification showed specific and sensitive results for schizophrenia, where two proteins (PRL and MRC2) produced adequate results.
Our results confirmed the utility of blood samples to identify protein signatures and mechanisms involved in the pathophysiology and treatment of SZ and BD.
精神分裂症（SZ）和双相情感障碍（BD）有许多共同特征：情绪和精神病性症状重叠、共同的遗传易感性、使用抗精神病药物（APs）治疗以及相似的代谢合并症。两者的病理生理学仍未明确界定，尚无生物标志物可用于临床诊断和管理。本研究旨在评估与停用APs 6个月的患者及健康对照（HCs）相比，服用APs的SZ和BD患者的血浆蛋白质组学概况。
我们使用功能富集、随机森林建模来识别潜在生物标志物，并使用多元回归分析与代谢异常的关联。
我们鉴定出几种已知在神经系统分化中起作用的蛋白质，如NTRK2、CNTN1、ROBO2和PLXNC1，这些蛋白质在未服用APs的SZ和BD患者中表达下调，但在服用APs的患者中“恢复正常”。其他蛋白质（如NCAM1和TNFRSF17）在未服用APs的患者中“正常”，但在服用APs的患者中表达下调，这表明这些变化与药物作用有关。我们发现主要在服用APs的SZ患者中，参与神经元可塑性的蛋白质有显著富集。大多数与代谢异常相关的蛋白质与APs的使用关系更大，而非与SZ或BD有关。生物标志物鉴定对精神分裂症显示出特异且敏感的结果，其中两种蛋白质（PRL和MRC2）产生了良好的结果。
我们的结果证实了血液样本在识别与SZ和BD的病理生理学及治疗相关的蛋白质特征和机制方面的效用。
