Metabolomic Analysis of Biochemical Changes in the Plasma and Urine of First-Episode Neuroleptic-Naive Schizophrenia Patients after Treatment with Risperidone
Metabolomic Analysis of Biochemical Changes in the Plasma and Urine of First-Episode Neuroleptic-Naive Schizophrenia Patients after Treatment with Risperidone
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DOI：
10.1021/pr300459d
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发表时间：
2012-08-01
影响因子：
4.4
通讯作者：
Ye, Hai-Sen
中科院分区：
文献类型：
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作者：
Cai, Hua-Lin;Li, Huan-De;Ye, Hai-Sen
7早期研究结果表明，大脑神经传递受损在精神分裂症的病理生理学中发挥着关键作用。最近在了解其多种病因和发病机制方面取得的进展提供了更多针对更广泛的躯体系统的推测假设。使用基于靶向串联质谱 (MS/MS) 的代谢组学平台，我们比较了首次发作抗精神病药初治精神分裂症患者 (FENNS) 和健康对照在 6 周利培酮单一疗法前后的血浆/尿液中由单胺和氨基酸神经递质 (NT) 代谢物组成的代谢特征，其中 表明患者的 NT 特征在治疗期间正在恢复。为了检测和识别与精神分裂症和利培酮治疗相关的潜在生物标志物，我们还对相同样本进行了组合超高效液相色谱质谱法 (UPLC-MS) 和基于 H-1 核磁共振 (NMR) 的代谢组学分析，表明患者的整体代谢特征与对照的进一步偏差。 NT 及其代谢物以及 32 种已鉴定的生物标志物表明 FENNS 中的 NT 代谢、氨基酸代谢、葡萄糖代谢、脂质代谢、能量代谢、抗氧化防御系统、肠道菌群和内分泌系统等代谢途径受到干扰。其中，孕二醇、柠檬酸盐和α-酮戊二酸（α-KG）与Bonferroni校正后的精神分裂症症状显着相关，可能是监测治疗效果的有用生物标志物。这些发现有望为精神分裂症的病理生理学提供有价值的见解，并可能推进精神分裂症及相关综合征的治疗、诊断和疾病预防方法。
7Early 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-naive 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 mass spectrometry (UPLC-MS) and H-1 nuclear magnetic resonance (NMR)-based metabolomic profiling of the same samples, indicating a further deviation of the patients' 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 a-ketoglutarate (alpha-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.