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

S Prabakaran; J E Swatton; M M Ryan; S J Huffaker; J T-J Huang; J L Griffin; M Wayland; T Freeman; F Dudbridge; K S Lilley; N A Karp; S Hester; D Tkachev; M L Mimmack; R H Yolken; M J Webster; E F Torrey; S Bahn

doi:10.1038/sj.mp.4001511

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

S Prabakaran, J E Swatton, M M Ryan, S J Huffaker, J T-J Huang, J L Griffin, M Wayland, T Freeman, F Dudbridge, K S Lilley, N A Karp, S Hester, D Tkachev, M L Mimmack, R H Yolken, M J Webster, E F Torrey, S Bahn

Royal (Dick) School of Veterinary Studies

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	684-97, 643
Journal	Molecular Psychiatry
Volume	9
Issue number	7
DOIs	https://doi.org/10.1038/sj.mp.4001511
Publication status	Published - Jul 2004

Keywords / Materials (for Non-textual outputs)

Brain
Fatty Acids
Genome, Human
Glucose
Humans
Hypoxia, Brain
Mitochondrial Diseases
Oligonucleotide Array Sequence Analysis
Oxidative Phosphorylation
Oxidative Stress
Proteomics
Schizophrenia
Signal Transduction

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10.1038/sj.mp.4001511

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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. (2004). Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Molecular Psychiatry, 9(7), 684-97, 643. https://doi.org/10.1038/sj.mp.4001511

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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 = "Brain, Fatty Acids, Genome, Human, Glucose, Humans, Hypoxia, Brain, Mitochondrial Diseases, Oligonucleotide Array Sequence Analysis, Oxidative Phosphorylation, Oxidative Stress, Proteomics, Schizophrenia, Signal Transduction",

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",

year = "2004",

month = jul,

doi = "10.1038/sj.mp.4001511",

language = "English",

volume = "9",

pages = "684--97, 643",

journal = "Molecular Psychiatry",

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Prabakaran, S, Swatton, JE, Ryan, MM, Huffaker, SJ, Huang, JT-J, Griffin, JL, Wayland, M, Freeman, T, Dudbridge, F, Lilley, KS, Karp, NA, Hester, S, Tkachev, D, Mimmack, ML, Yolken, RH, Webster, MJ, Torrey, EF & Bahn, S 2004, 'Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress', Molecular Psychiatry, vol. 9, no. 7, pp. 684-97, 643. https://doi.org/10.1038/sj.mp.4001511

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T2 - evidence for compromised brain metabolism and oxidative stress

AU - Prabakaran, S

AU - Swatton, J E

AU - Ryan, M M

AU - Huffaker, S J

AU - Huang, J T-J

AU - Griffin, J L

AU - Wayland, M

AU - Freeman, T

AU - Dudbridge, F

AU - Lilley, K S

AU - Karp, N A

AU - Hester, S

AU - Tkachev, D

AU - Mimmack, M L

AU - Yolken, R H

AU - Webster, M J

AU - Torrey, E F

AU - Bahn, S

PY - 2004/7

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AB - 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.

KW - Brain

KW - Fatty Acids

KW - Genome, Human

KW - Glucose

KW - Humans

KW - Hypoxia, Brain

KW - Mitochondrial Diseases

KW - Oligonucleotide Array Sequence Analysis

KW - Oxidative Phosphorylation

KW - Oxidative Stress

KW - Proteomics

KW - Schizophrenia

KW - Signal Transduction

U2 - 10.1038/sj.mp.4001511

DO - 10.1038/sj.mp.4001511

M3 - Article

C2 - 15098003

SN - 1359-4184

VL - 9

SP - 684-97, 643

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 7

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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