Stratification and prediction of remission in first-episode psychosis patients: the OPTiMiSE cohort study
Stratification and prediction of remission in first-episode psychosis patients: the OPTiMiSE cohort study
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DOI：
10.1038/s41398-018-0366-5
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发表时间：
2019-01-17
影响因子：
6.8
通讯作者：
Sommer, I. E.
中科院分区：
文献类型：
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作者：
Martinuzzi, Emanuela;Barbosa, Susana;Sommer, I. E.
一线抗精神病药物治疗的早期反应与精神病患者的长期症状和功能结局密切相关。不幸的是，试图确定可靠的预测治疗反应的首发精神病（FEP）患者尚未成功。其中一个原因可能是FEP患者在症状表达和潜在疾病生物学机制方面具有高度异质性，从而阻碍了治疗反应的一刀切预测因素的识别。我们使用聚类方法将325例FEP患者分为四个临床亚型，称为C1 A，C1 B，C2 A和C2B，根据他们的症状使用阳性和阴性综合征量表（PANSS）量表进行评估。与C1 B，C2 A和C2B患者相比，C1 A亚型患者表现出最严重的症状，并且在使用第二代抗精神病药物氨磺必利治疗时最有可能成为非缓解者。在治疗前，C1 A患者表现出较高的血清水平的几种促炎细胞因子和炎症相关的生物标志物，因此验证了我们的分层方法的外部生物措施。最重要的是，在C1 A亚型中，而不是其他亚型中，血清白细胞介素（IL）-15水平较低，血清C-X-C基序趋化因子12（CXCL 12）水平较高，既往接触巨细胞病毒（CMV），使用娱乐性药物和年龄较小均与治疗后4周非缓解者的几率较高相关。该模型的预测值良好（平均曲线下面积（AUC）= 0.73 +/- 0.10），其特异性和灵敏度分别为45 +/- 0.09%和83 +/-0.03%。这些结果在临床试验中的进一步验证和复制将为开发基于血液的精神病辅助临床决策支持系统铺平道路。
Early response to first-line antipsychotic treatments is strongly associated with positive long-term symptomatic and functional outcome in psychosis. Unfortunately, attempts to identify reliable predictors of treatment response in first-episode psychosis (FEP) patients have not yet been successful. One reason for this could be that FEP patients are highly heterogeneous in terms of symptom expression and underlying disease biological mechanisms, thereby impeding the identification of one-size-fits-all predictors of treatment response. We have used a clustering approach to stratify 325 FEP patients into four clinical subtypes, termed C1A, C1B, C2A and C2B, based on their symptoms assessed using the Positive and Negative Syndrome Scale (PANSS) scale. Compared to C1B, C2A and C2B patients, those from the C1A subtype exhibited the most severe symptoms and were the most at risk of being non-remitters when treated with the second-generation antipsychotic drug amisulpride. Before treatment, C1A patients exhibited higher serum levels of several pro-inflammatory cytokines and inflammation-associated biomarkers therefore validating our stratification approach on external biological measures. Most importantly, in the C1A subtype, but not others, lower serum levels of interleukin (IL)-15, higher serum levels of C-X-C motif chemokine 12 (CXCL12), previous exposure to cytomegalovirus (CMV), use of recreational drugs and being younger were all associated with higher odds of being non-remitters 4 weeks after treatment. The predictive value of this model was good (mean area under the curve (AUC) = 0.73 +/- 0.10), and its specificity and sensitivity were 45 +/- 0.09% and 83 +/- 0.03%, respectively. Further validation and replication of these results in clinical trials would pave the way for the development of a blood-based assisted clinical decision support system in psychosis.