Association of Complement and Coagulation Pathway Proteins With Treatment Response in First-Episode Psychosis: A Longitudinal Analysis of the OPTiMiSE Clinical Trial.
Association of Complement and Coagulation Pathway Proteins With Treatment Response in First-Episode Psychosis: A Longitudinal Analysis of the OPTiMiSE Clinical Trial.
复制标题
补体和凝血途径蛋白与首发精神病治疗反应的相关性：OPTiMiSE临床试验的纵向分析。
DOI：
10.1093/schbul/sbac201
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发表时间：
2023-07-04
影响因子：
6.6
通讯作者：
McGuire, Philip
中科院分区：
文献类型：
--
作者：
Susai, Subash Raj;Foecking, Melanie;Mongan, David;Heurich, Meike;Coutts, Fiona;Egerton, Alice;Whetton, Tony;Winter-van Rossum, Inge;Unwin, Richard D.;Pollak, Thomas A.;Weiser, Mark;Leboyer, Marion;Rujescu, Dan;Byrne, Jonah F.;Gifford, George W.;Dazzan, Paola;Koutsouleris, Nikolaos;Kahn, Rene S.;Cotter, David R.;McGuire, Philip
关键词：
单从临床上很难预测对特定抗精神病药物的治疗反应。本研究假设基线补体途径活性可预测治疗反应，并研究基线血浆生物标志物与抗精神病药物治疗反应之间的关系。 基线血浆样品从多中心临床试验的首次发作的精神病患者（n = 243）收集。参与者接受氨磺必利治疗4周。使用数据依赖性和数据独立性质谱法测量基线时的补体和凝血蛋白水平。主要结局是4周时的缓解状态，次要结局包括治疗期间精神病性和功能性症状的变化。此外，在基线时对补体C1 R以及活化标志物C4 a和sC 5 b-9进行免疫测定。 补体C4 A的血浆水平与4周时的缓解显著相关。此外，较高水平的几种补体和凝血途径蛋白与精神病症状的减少和功能的改善有关。免疫测定显示C1 R和C4 a的基线水平以及补体激活标志物sC 5 b-9水平与治疗反应相关。 结果表明，抗精神病药物治疗的反应可能与治疗前血浆补体和凝血途径蛋白的水平有关。这与将免疫功能障碍与精神病的病理生理学联系起来的独立证据相一致。此外，这些结果为开发针对精神病补体系统的新型治疗方法提供了信息。
Treatment response to specific antipsychotic medications is difficult to predict on clinical grounds alone. The current study hypothesizes that the baseline complement pathway activity predicts the treatment response and investigates the relationship between baseline plasma biomarkers with treatment response to antipsychotic medications. Baseline plasma samples were collected from first episode of psychosis patients (n = 243) from a multi-center clinical trial. The participants were treated with amisulpride for 4 weeks. Levels of complement and coagulation proteins at baseline were measured using both data-dependent and data-independent mass spectrometry approaches. The primary outcome was remission status at 4 weeks and the secondary outcomes included change in psychotic and functional symptoms over the period of treatment. In addition, immunoassays were performed at baseline for complement C1R, as well as for activation markers C4a and sC5b-9. The plasma level of complement variant C4A was significantly associated with remission at 4 weeks. Moreover, higher levels of several complement and coagulation pathway proteins were associated with a reduction in psychotic symptoms and an improvement in functioning. Immunoassays showed an association of baseline levels of C1R and C4a as well as complement activation marker sC5b-9 levels with treatment response. The results demonstrated that the response to antipsychotic treatment might be related to pre-treatment levels of plasma complement and coagulation pathway proteins. This is consistent with independent evidence associating immune dysfunction with the pathophysiology of psychosis. Moreover, these results inform the development of novel therapeutic approaches that target the complement system for psychosis.
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影响因子：
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作者：
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影响因子：
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