Determination of steroid metabolome as a possible tool for laboratory diagnosis of schizophrenia
Determination of steroid metabolome as a possible tool for laboratory diagnosis of schizophrenia
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DOI：
10.1016/j.jsbmb.2012.08.009
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发表时间：
2013-01-01
影响因子：
4.1
通讯作者：
Hampl, Richard
中科院分区：
文献类型：
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作者：
Bicikova, Marie;Hill, Martin;Hampl, Richard
代谢组学研究代表了精神分裂症早期诊断的一个有前途的工具。本研究的目的是发现患者和对照组类固醇谱的差异，并通过建立基于类固醇数据的预测模型来评估精神分裂症的诊断。采用气相色谱-质谱联用技术测定了22例未用药患者的22种神经活性甾体及其代谢产物和17种极性结合物（首次发作）精神分裂症患者（13名男性和9名女性）在使用非典型抗精神病药物治疗6个月之前和之后。将结果与健康受试者（22名男性，25名女性）的数据进行比较。总之，发现以下显著差异：（1）在两种性别中，在患者中发现较高水平的硫酸双烯醇酮和孕酮代谢途径中C21-类固醇的硫酸化5 α-和5 β-饱和代谢物，表明硫酸酯酶活性降低。(2)在少数情况下，在患者中发现C21类固醇的相应5 α-代谢物水平降低。(3)就C19类固醇而言，在两种性别患者中，5 β还原代谢物的水平显著降低。另一方面，除了少数例外，治疗对大多数类固醇水平没有显着影响。此外，为了评估精神分裂症状态和类固醇水平之间的关系，并建立精神分裂症的预测模型，应用了降维的多变量回归（正交投影到潜在结构的方法，OPLS）。无论患者数量如何，使用该模型使我们能够以几乎100%的灵敏度来诊断精神分裂症。我们的研究结果表明，类固醇水平的评估可能成为精神病学中有效且准确的实验室测试。我们研究的一个局限性是没有被诊断为精神分裂症以外的受试者，因此我们无法得出结论，该结果是否对精神分裂症具有特异性。另一方面，类固醇代谢组学模型可作为进一步研究的诊断工具。(C)2012爱思唯尔有限公司保留所有权利。
Metabolomic studies represent a promising tool for early diagnosis of schizophrenia. The aim of this study was to find differences in the steroid spectrum in patients and controls, and to assess the diagnosis of schizophrenia by building a predictive model based on steroid data.Thirty-nine serum steroids (22 neuroactive steroids and their metabolites and 17 polar conjugates) representing steroid metabolome were measured by gas chromatography-mass spectrometry in 22 drug-naive (first episode) schizophrenia patients (13 men and 9 women) before and after six-month treatment with atypical antipsychotics. The results were compared to the data from healthy subjects (22 males, 25 females). In summary the following significant differences were found: (1) In both sexes higher levels of pregnenolone sulfate and sulfated 5 alpha- as well as 5 beta-saturated metabolites of C21-steroids in progesterone metabolic pathway were found in patients, pointing to decreased activity of sulfatase. (2) In a few instances decreased levels of the respective 5 alpha-metabolites of C21 steroids were found in patients. (3) As C19 steroids concern, in both sexes there were considerably lowered levels of 5 beta-reduced metabolites in patients. On the other hand, with only a few exceptions, the treatment did not significantly influence most steroid levels. Further, to assess the relationships between schizophrenia status and steroid levels and to build the predictive model of schizophrenia, multivariate regression with reduction of dimensionality (the method of orthogonal projections to latent structures, OPLS) was applied. Irrespective of the small number of patients, use of this model enabled us to state the diagnosis of schizophrenia with almost 100% sensitivity.Our findings suggest that the assessment of steroid levels may become a valid and accurate laboratory test in psychiatry. A limitation of our study is the absence of subjects with a diagnosis other than schizophrenia, so we cannot conclude whether the results are specific for schizophrenia. On the other hand, steroid metabolome model may be used as a diagnostic tool for further studies. (C) 2012 Elsevier Ltd. All rights reserved.