Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress.
Sudhakaran Prabakaran,Sudhakaran Prabakaran,J. E. Swatton,J. E. Swatton,Margaret Ryan,Margaret Ryan,S. J. Huffaker,S. J. Huffaker,Jeffrey T.-J. Huang,Jeffrey T.-J. Huang,Julian L. Griffin,Matthew T. Wayland,Tom C. Freeman,Frank Dudbridge,Kathryn S. Lilley,Natasha A. Karp,Svenja Hester,D. Tkachev,D. Tkachev,Michael L. Mimmack,Michael L. Mimmack,Robert H. Yolken,Maree J. Webster,E F Torrey,Sabine Bahn,Sabine Bahn +25 more
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TLDR
It is proposed that oxidative stress and the ensuing cellular adaptations are linked to the schizophrenia disease process and it is hoped that this new disease concept may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.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.read more
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Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence.
TL;DR: This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry.
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Oxidative stress in psychiatric disorders : evidence base and therapeutic implications
TL;DR: Multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders and suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders, but also introduce new targets for the development of therapeutic interventions.
Journal ArticleDOI
Long-chain ω-3 fatty acids for indicated prevention of psychotic disorders: A randomized, placebo-controlled trial
G. Paul Amminger,Miriam R. Schäfer,Konstantinos Papageorgiou,Claudia M. Klier,Sue M. Cotton,Susan Harrigan,Andrew Mackinnon,Patrick D. McGorry,Gregor Berger +8 more
TL;DR: Long-chain omega-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states.
Journal ArticleDOI
Epigenomic Profiling Reveals DNA-Methylation Changes Associated with Major Psychosis
Jonathan Mill,Thomas Tang,Zachary Kaminsky,Tarang Khare,Simin Yazdanpanah,Luigi Bouchard,Luigi Bouchard,Peixin Jia,Abbas Assadzadeh,James M. Flanagan,James M. Flanagan,Axel Schumacher,Axel Schumacher,Sun Chong Wang,Sun Chong Wang,Arturas Petronis +15 more
TL;DR: This study uses CpG-island microarrays to identify DNA-methylation changes in the frontal cortex and germline associated with schizophrenia and bipolar disorder and reports evidence for a strong correlation between DNA methylation in the MEK1 gene promoter region and lifetime antipsychotic use in schizophrenia patients.
Journal ArticleDOI
Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy
Warwick B. Dunn,David Broadhurst,Helen J. Atherton,Helen J. Atherton,Royston Goodacre,Julian L. Griffin +5 more
TL;DR: An introduction to metabolites, metabolomes, metabolomics and the role of MS and NMR spectroscopy will be provided and the applications of metabolomics in mammalian systems biology for the study of the health-disease continuum, drug efficacy and toxicity and dietary effects on mammalian health will be reviewed.
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