@article{a1f860c63b0e4011a02c199ca56de11f,
title = "Mitochondrial dysfunction in schizophrenia: Evidence for compromised brain metabolism and oxidative stress",
abstract = "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.",
keywords = "Functional genomics, Gene ontology, Mitochondria, Oxidative stress, Schizophrenia, Systems-based approach",
author = "S. Prabakaran and Swatton, {J. E.} and Ryan, {M. M.} and Huffaker, {S. J.} and Huang, {J. T.J.} and Griffin, {J. L.} and M. Wayland and T. Freeman and F. Dudbridge and Lilley, {K. S.} and Karp, {N. A.} and S. Hester and D. Tkachev and Mimmack, {M. L.} and Yolken, {R. H.} and Webster, {M. J.} and Torrey, {E. F.} and S. Bahn",
note = "Funding Information: This research was supported by the Stanley Medical Research Institute (SMRI) and the donations of the Stanley brain collection courtesy of Drs Michael B Knable, E Fuller Torrey, Maree J Webster, Serge Weis and Robert H Yolken. The Department of Psychiatry gratefully acknowledges SMRI center support. We thank all other members of the Bahn laboratory for intellectual and practical input. Many thanks to Professors Peter Jones and Steve O{\textquoteright}Rahilly and Dr Husseini Manji for valuable input and discussions and Dr Vivian Lee for help with gene ontology analysis. Sudhakaran Prabakaran is supported through a Nehru and Cambridge Commonwealth Trust scholarship, Dmitri Tkachev through a Darwin Trust scholarship, Janie Swatton is a Community Fund/Alzheimer Research Trust fellow and Stephen Huffaker is supported by the National Institutes of Health-Cambridge Health Science Scholars Program. We thank Drs Brian Sweatman and John Haselden of GlaxoSmithKline, Ware, UK for generous access to high-resolution NMR facilities. We also thank MRC genservice for hybridisation of the arrays.",
year = "2004",
month = jul,
doi = "10.1038/sj.mp.4001511",
language = "English (US)",
volume = "9",
pages = "684--697",
journal = "Molecular psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "7",
}