Schizophrenia shows a unique metabolomics signature in plasma.
Schizophrenia shows a unique metabolomics signature in plasma.
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DOI：
10.1038/tp.2012.76
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发表时间：
2012-08-14
影响因子：
6.8
通讯作者：
Rujescu D
中科院分区：
文献类型：
--
作者：
He Y;Yu Z;Giegling I;Xie L;Hartmann AM;Prehn C;Adamski J;Kahn R;Li Y;Illig T;Wang-Sattler R;Rujescu D
精神分裂症是一种严重的复杂精神障碍，影响着世界人口的0.5%-1%。到目前为止，对这种疾病的诊断主要是基于个人，因此是主观的访谈。精神分裂症的潜在分子机制尚不清楚。利用靶向代谢组学，我们量化和比较了216名健康对照和265名精神分裂症患者血浆样本中的103种代谢物，其中包括52例不服用抗精神病药物的患者。与健康对照组比较，精神分裂症患者(P值范围为2.9×10−8~2.5×10−4)和非抗精神病药先证者(P值范围为0.006.0 5~0.0 3)的5种代谢物水平均有显著变化。这些代谢物包括四种氨基酸(精氨酸、谷氨酰胺、组氨酸和鸟氨酸)和一种脂类(PC ae C38：6)，被认为是精神分裂症的候选生物标志物。为了探索相关代谢途径的遗传易感性，我们构建了一个将这五种异常代谢物与13个精神分裂症危险基因连接起来的分子网络。我们的结果表明，与谷氨酰胺和精氨酸代谢相关的生物合成途径及其相关信号通路的异常可能是遗传风险因素，可能与精神分裂症相关的病理机制和记忆障碍有关。这项研究表明，在血浆中检测到的代谢偏差可以作为潜在的生物标志物来辅助精神分裂症的诊断。
Schizophrenia is a severe complex mental disorder affecting 0.5–1% of the world population. To date, diagnosis of the disease is mainly based on personal and thus subjective interviews. The underlying molecular mechanism of schizophrenia is poorly understood. Using targeted metabolomics we quantified and compared 103 metabolites in plasma samples from 216 healthy controls and 265 schizophrenic patients, including 52 cases that do not take antipsychotic medication. Compared with healthy controls, levels of five metabolites were found significantly altered in schizophrenic patients (P-values ranged from 2.9 × 10−8 to 2.5 × 10−4) and in neuroleptics-free probands (P-values ranging between 0.006 and 0.03), respectively. These metabolites include four amino acids (arginine, glutamine, histidine and ornithine) and one lipid (PC ae C38:6) and are suggested as candidate biomarkers for schizophrenia. To explore the genetic susceptibility on the associated metabolic pathways, we constructed a molecular network connecting these five aberrant metabolites with 13 schizophrenia risk genes. Our result implicated aberrations in biosynthetic pathways linked to glutamine and arginine metabolism and associated signaling pathways as genetic risk factors, which may contribute to patho-mechanisms and memory deficits associated with schizophrenia. This study illustrated that the metabolic deviations detected in plasma may serve as potential biomarkers to aid diagnosis of schizophrenia.
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影响因子：
30.8
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通讯作者：
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影响因子：
4.8
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Athanasiu L;Mattingsdal M;Kähler AK;Brown A;Gustafsson O;Agartz I;Giegling I;Muglia P;Cichon S;Rietschel M;Pietiläinen OP;Peltonen L;Bramon E;Collier D;Clair DS;Sigurdsson E;Petursson H;Rujescu D;Melle I;Steen VM;Djurovic S;Andreassen OA
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Andreassen OA
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Kastenmueller, Gabi;Roemisch-Margl, Werner;Suhre, Karsten
通讯作者：
Suhre, Karsten
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3.7
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通讯作者：
Muglia P
影响因子：
6.8
作者：
Braunewell KH;Dwary AD;Richter F;Trappe K;Zhao C;Giegling I;Schönrath K;Rujescu D
通讯作者：
Rujescu D