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 (Lead / Corresponding author)

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

563 Citations (Scopus)

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)	684-697
Number of pages	14
Journal	Molecular Psychiatry
Volume	9
Issue number	7
Early online date	20 Apr 2004
DOIs	https://doi.org/10.1038/sj.mp.4001511
Publication status	Published - Jul 2004

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Functional genomics
Gene ontology
Mitochondria
Oxidative stress
Schizophrenia
Systems-based approach

ASJC Scopus subject areas

Molecular Biology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

Access to Document

10.1038/sj.mp.4001511

Cite this

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), 684-697. https://doi.org/10.1038/sj.mp.4001511

@article{c36d9e358bc945c48ce697dba6a07a91,

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",

year = "2004",

month = jul,

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

language = "English",

volume = "9",

pages = "684--697",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer Nature",

number = "7",

}

Prabakaran, S, Swatton, JE, Ryan, MM, Huffaker, SJ, Huang, JTJ, 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. 684-697. https://doi.org/10.1038/sj.mp.4001511

TY - JOUR

T1 - Mitochondrial dysfunction in schizophrenia

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

Y1 - 2004/7

N2 - 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.

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 - Functional genomics

KW - Gene ontology

KW - Mitochondria

KW - Oxidative stress

KW - Schizophrenia

KW - Systems-based approach

U2 - 10.1038/sj.mp.4001511

DO - 10.1038/sj.mp.4001511

M3 - Article

C2 - 15098003

AN - SCOPUS:3142745187

SN - 1359-4184

VL - 9

SP - 684

EP - 697

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 7

ER -

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

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

Fingerprint

Cite this