Metabolomic Analysis of Biochemical Changes in the Plasma and Urine of First-Episode Neuroleptic-Na茂ve Schizophrenia Patients after Treatment with Risperidone
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- 作者：Hua-Lin Cai ; Huan-De Li ; Xian-Zhong Yan ; Bo Sun ; Qi Zhang ; Miao Yan ; Wen-Yuan Zhang ; Pei Jiang ; Rong-Hua Zhu ; Yi-Ping Liu ; Ping-Fei Fang ; Ping Xu ; Hai-Yan Yuan ; Xiang-Hui Zhang ; Li Hu ; Wen Yang ; Hai-Sen Ye
- 刊名：Journal of Proteome Research
- 出版年：2012
- 出版时间：August 3, 2012
- 年：2012
- 卷：11
- 期：8
- 页码：4338-4350
- 全文大小：546K
- 年卷期：v.11,no.8(August 3, 2012)
- ISSN：1535-3907
文摘
Early findings propose that impaired neurotransmission in the brain plays a key role in the pathophysiology of schizophrenia. Recent advances in understanding its multiple etiologies and pathogenetic mechanisms provide more speculative hypotheses focused on even broader somatic systems. Using a targeted tandem mass spectrometry (MS/MS)-based metabolomic platform, we compared metabolic signatures consisting of monoamine and amino acid neurotransmitter (NT) metabolites in plasma/urine simultaneously between first-episode neuroleptic-na茂ve schizophrenia patients (FENNS) and healthy controls before and after a 6-week risperidone monotherapy, which suggest that the patient NT profiles are restoring during treatment. To detect and identify potential biomarkers associated with schizophrenia and risperidone treatment, we also performed a combined ultraperformance liquid chromatography鈥搈ass spectrometry (UPLC鈥揗S) and 1H nuclear magnetic resonance (NMR)-based metabolomic profiling of the same samples, indicating a further deviation of the patients鈥?global metabolic profile from that of controls. The NTs and their metabolites together with the 32 identified biomarkers underpin that metabolic pathways including NT metabolism, amino acid metabolism, glucose metabolism, lipid metabolism, energy metabolism, antioxidant defense system, bowel microflora and endocrine system are disturbed in FENNS. Among them, pregnanediol, citrate and 伪-ketoglutarate (伪-KG) were significantly associated with symptomatology of schizophrenia after Bonferroni correction and may be useful biomarkers for monitoring therapeutic efficacy. These findings promise to yield valuable insights into the pathophysiology of schizophrenia and may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.