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.
authors.affiliation: Department of Neurobiology, Babraham Institute, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Prabakaran
authors.forename: J E
authors.initials: JE
authors.lastname: Swatton
authors.forename: M M
authors.initials: MM
authors.lastname: Ryan
authors.forename: S J
authors.initials: SJ
authors.lastname: Huffaker
authors.forename: J T-J
authors.initials: JT
authors.lastname: Huang
authors.forename: J L
authors.initials: JL
authors.lastname: Griffin
authors.forename: M
authors.initials: M
authors.lastname: Wayland
authors.forename: T
authors.initials: T
authors.lastname: Freeman
authors.forename: F
authors.initials: F
authors.lastname: Dudbridge
authors.forename: K S
authors.initials: KS
authors.lastname: Lilley
authors.forename: N A
authors.initials: NA
authors.lastname: Karp
authors.forename: S
authors.initials: S
authors.lastname: Hester
authors.forename: D
authors.initials: D
authors.lastname: Tkachev
authors.forename: M L
authors.initials: ML
authors.lastname: Mimmack
authors.forename: R H
authors.initials: RH
authors.lastname: Yolken
authors.forename: M J
authors.initials: MJ
authors.lastname: Webster
authors.forename: E F
authors.initials: EF
authors.lastname: Torrey
authors.forename: S
authors.initials: S
authors.lastname: Bahn
mesh_terms: D001921:Brain / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D015894:Genome, Human; D005947:Glucose / Q000378:metabolism; D006801:Humans; D002534:Hypoxia, Brain / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D040901:Proteomics; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005227:Fatty Acids; D005947:Glucose