Prabakaran S, Swatton J E, Ryan M M, Huffaker S J, Huang J T-J, Griffin J L, Wayland M, Freeman T, Dudbridge F, Lilley K S, Karp N A, Hester S, Tkachev D, Mimmack M L, Yolken R H, Webster M J, Torrey E F, Bahn S
Department of Neurobiology, Babraham Institute, Cambridge, UK.
Mol Psychiatry. 2004 Jul;9(7):684-97, 643. doi: 10.1038/sj.mp.4001511.
The etiology and pathophysiology of schizophrenia remain unknown. A parallel transcriptomics, proteomics and metabolomics approach was employed on human brain tissue to explore the molecular disease signatures. Almost half the altered proteins identified by proteomics were associated with mitochondrial function and oxidative stress responses. This was mirrored by transcriptional and metabolite perturbations. Cluster analysis of transcriptional alterations showed that genes related to energy metabolism and oxidative stress differentiated almost 90% of schizophrenia patients from controls, while confounding drug effects could be ruled out. We propose that oxidative stress and the ensuing cellular adaptations are linked to the schizophrenia disease process and hope that this new disease concept may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.
精神分裂症的病因和病理生理学仍然未知。我们采用转录组学、蛋白质组学和代谢组学并行的方法对人脑组织进行研究，以探索分子疾病特征。蛋白质组学鉴定出的几乎一半改变的蛋白质与线粒体功能和氧化应激反应相关。转录和代谢物扰动也反映了这一点。转录改变的聚类分析表明，与能量代谢和氧化应激相关的基因能够将近90%的精神分裂症患者与对照组区分开来，同时可以排除混杂的药物影响。我们认为氧化应激及随之而来的细胞适应性变化与精神分裂症的疾病进程有关，希望这一新的疾病概念能够推动精神分裂症及相关综合征的治疗、诊断和疾病预防方法的发展。
