Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China.
J Proteome Res. 2011 Dec 2;10(12):5433-43. doi: 10.1021/pr2006796. Epub 2011 Nov 8.
Despite recent advances in understanding the pathophysiology of schizophrenia and the mechanisms of antipsychotic drug action, the development of biomarkers for diagnosis and therapeutic monitoring in schizophrenia remains challenging. Metabolomics provides a powerful approach to discover diagnostic and therapeutic biomarkers by analyzing global changes in an individual's metabolic profile in response to pathophysiological stimuli or drug intervention. In this study, we performed gas chromatography-mass spectrometry based metabolomic profiling in serum of unmedicated schizophrenic patients before and after an 8-week risperidone monotherapy, to detect potential biomarkers associated with schizophrenia and risperidone treatment. Twenty-two marker metabolites contributing to the complete separation of schizophrenic patients from matched healthy controls were identified, with citrate, palmitic acid, myo-inositol, and allantoin exhibiting the best combined classification performance. Twenty marker metabolites contributing to the complete separation between posttreatment and pretreatment patients were identified, with myo-inositol, uric acid, and tryptophan showing the maximum combined classification performance. Metabolic pathways including energy metabolism, antioxidant defense systems, neurotransmitter metabolism, fatty acid biosynthesis, and phospholipid metabolism were found to be disturbed in schizophrenic patients and partially normalized following risperidone therapy. Further study of these metabolites may facilitate the development of noninvasive biomarkers and more efficient therapeutic strategies for schizophrenia.
尽管近年来在理解精神分裂症的病理生理学和抗精神病药物作用机制方面取得了进展，但开发用于精神分裂症诊断和治疗监测的生物标志物仍然具有挑战性。代谢组学通过分析个体代谢谱对病理生理刺激或药物干预的全球变化，提供了一种发现诊断和治疗生物标志物的强大方法。在这项研究中，我们对未经治疗的精神分裂症患者在接受 8 周利培酮单药治疗前后的血清进行了基于气相色谱-质谱的代谢组学分析，以检测与精神分裂症和利培酮治疗相关的潜在生物标志物。鉴定出 22 种与精神分裂症患者和匹配的健康对照组完全分离相关的标记代谢物，其中柠檬酸、棕榈酸、肌醇和尿囊素表现出最佳的组合分类性能。鉴定出 20 种与治疗后和治疗前患者完全分离相关的标记代谢物，其中肌醇、尿酸和色氨酸表现出最大的组合分类性能。发现精神分裂症患者的能量代谢、抗氧化防御系统、神经递质代谢、脂肪酸生物合成和磷脂代谢等代谢途径发生紊乱，利培酮治疗后部分恢复正常。对这些代谢物的进一步研究可能有助于开发非侵入性生物标志物和更有效的精神分裂症治疗策略。
