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Molecular Psychiatry (2004) 9, 643. doi:10.1038/sj.mp.4001532

Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress

S Prabakaran1,2,8, J E Swatton1,2,8, M M Ryan1,2,8, S J Huffaker1,2,8, J T-J Huang1,2, J L Griffin3, M Wayland4, T Freeman4, F Dudbridge4, K S Lilley5, N A Karp5, S Hester5, D Tkachev1,2, M L Mimmack1,2, R H Yolken6, M J Webster7, E F Torrey7 and S Bahn1,2

  1. 1Department of Neurobiology, Babraham Institute, Cambridge, UK
  2. 2Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
  3. 3Department of Biochemistry, University of Cambridge, Sanger Building, Cambridge, UK
  4. 4MRC Rosalind Franklin Centre for Genomics Research (formerly MRC Human Genome Mapping Project Resource Centre), Hinxton, Cambridge, UK
  5. 5Department of Biochemistry, Cambridge Centre for Proteomics, University of Cambridge, Cambridge, UK
  6. 6Stanley Division of Developmental Neurovirology, Johns Hopkins School of Medicine, Baltimore, MD, USA
  7. 7Stanley Laboratory of Brain Research, Department of Psychiatry, Uniformed Services University for the Health Sciences, Bethesda, MD, USA

8These authors contributed equally to this work

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Transcript changes and altered pathways in schizophrenia prefrontal cortex. (a) Mitochondria are the most affected cellular components at the transcript level in schizophrenia. Cellular localization of the significantly altered genes (both up- and downregulated) that passed RMA and filtering procedures were analyzed and visualized using GO Surfer (http://biosun1.harvard.edu/complab/gosurfer/). Branches and nodes represent pathways containing greater than five genes. Significantly altered 'cellular components' (P<0.05) are highlighted in red and their categories are indicated. (b) Metabolic categories found to be most significantly altered at the transcript level. EASE (http://david.niaid.nih.gov/david/ease.htm) was used for pathway analysis of microarray results and to determine significantly up- and/or downregulated GO biological processes and KEGG metabolic pathways. (c) Hierarchical clustering tree of schizophrenia (vertical blue lines) and controls (vertical gray lines) microarray chips on the basis of 59 significantly altered genes related to energy metabolism and oxidative stress. Drug-naive schizophrenia patients are denoted by ** (n=7), while minimally treated patients are marked by * (<6000 lifetime fluphenazine units; n=4). Note that the schizophrenia group appears to fall into two subclusters with respect to lowered transcript expression as indicated by the prominent blue shading. For more information on this topic, please see the article by Prabakaran et al on pp 684–697.

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