Polygenic Risk Scores for Subtyping of Schizophrenia.

IF 3.6 Q1 PSYCHIATRY Schizophrenia Research and Treatment Pub Date : 2020-07-23 eCollection Date: 2020-01-01 DOI:10.1155/2020/1638403
Jingchun Chen, Travis Mize, Jain-Shing Wu, Elliot Hong, Vishwajit Nimgaonkar, Kenneth S Kendler, Daniel Allen, Edwin Oh, Alison Netski, Xiangning Chen
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引用次数: 6

Abstract

Schizophrenia is a complex disorder with many comorbid conditions. In this study, we used polygenic risk scores (PRSs) from schizophrenia and comorbid traits to explore consistent cluster structure in schizophrenia patients. With 10 comorbid traits, we found a stable 4-cluster structure in two datasets (MGS and SSCCS). When the same traits and parameters were applied for the patients in a clinical trial of antipsychotics, the CATIE study, a 5-cluster structure was observed. One of the 4 clusters found in the MGS and SSCCS was further split into two clusters in CATIE, while the other 3 clusters remained unchanged. For the 5 CATIE clusters, we evaluated their association with the changes of clinical symptoms, neurocognitive functions, and laboratory tests between the enrollment baseline and the end of Phase I trial. Class I was found responsive to treatment, with significant reduction for the total, positive, and negative symptoms (p = 0.0001, 0.0099, and 0.0028, respectively), and improvement for cognitive functions (VIGILANCE, p = 0.0099; PROCESSING SPEED, p = 0.0006; WORKING MEMORY, p = 0.0023; and REASONING, p = 0.0015). Class II had modest reduction of positive symptoms (p = 0.0492) and better PROCESSING SPEED (p = 0.0071). Class IV had a specific reduction of negative symptoms (p = 0.0111) and modest cognitive improvement for all tested domains. Interestingly, Class IV was also associated with decreased lymphocyte counts and increased neutrophil counts, an indication of ongoing inflammation or immune dysfunction. In contrast, Classes III and V showed no symptom reduction but a higher level of phosphorus. Overall, our results suggest that PRSs from schizophrenia and comorbid traits can be utilized to classify patients into subtypes with distinctive clinical features. This genetic susceptibility based subtyping may be useful to facilitate more effective treatment and outcome prediction.

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精神分裂症亚型的多基因风险评分。
精神分裂症是一种复杂的疾病,有许多合并症。在这项研究中,我们使用来自精神分裂症和共病特征的多基因风险评分(PRSs)来探索精神分裂症患者中一致的聚类结构。我们在两个数据集(MGS和SSCCS)中发现了10个共病特征的稳定的4簇结构。当相同的特征和参数应用于抗精神病药物临床试验的患者时,CATIE研究,观察到一个5簇结构。在MGS和SSCCS中发现的4个簇中的一个在CATIE中进一步分成两个簇,而其他3个簇保持不变。对于5个CATIE集群,我们评估了它们在入组基线和I期试验结束期间与临床症状、神经认知功能和实验室测试变化的相关性。I类患者对治疗有反应,总症状、阳性症状和阴性症状显著减少(p分别= 0.0001、0.0099和0.0028),认知功能改善(警惕性,p = 0.0099;处理速度,p = 0.0006;工作记忆,p = 0.0023;推理,p = 0.0015)。II类患者阳性症状轻度减轻(p = 0.0492),处理速度更快(p = 0.0071)。IV类患者的阴性症状明显减少(p = 0.0111),所有测试领域的认知能力均有适度改善。有趣的是,IV类也与淋巴细胞计数减少和中性粒细胞计数增加有关,这是持续炎症或免疫功能障碍的指示。相比之下,III类和V类没有症状减轻,但磷水平较高。总的来说,我们的研究结果表明,精神分裂症的PRSs和共病特征可以用来将患者分为具有不同临床特征的亚型。这种基于遗传易感性的亚型可能有助于促进更有效的治疗和预后预测。
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来源期刊
CiteScore
4.60
自引率
0.00%
发文量
2
审稿时长
14 weeks
期刊介绍: Schizophrenia Research and Treatment is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies related to all aspects of schizophrenia.
期刊最新文献
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