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Neurosci Biobehav Rev. 2015 Jan;48:10-21. doi: 10.1016/j.neubiorev.2014.11.005. Epub 2014 Nov 15.

Mitochondrial dysfunction in schizophrenia: pathways, mechanisms and implications.

Author information

1
Department of Human Genetics, National Institute of Mental Health & Neurosciences, Bangalore 560029, India.
2
Translational Psychiatry Laboratory, Neurobiology Research Centre and Department of Psychiatry, National Institute of Mental Health & Neurosciences, Bangalore, 560029, India.
3
IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia; Department of Psychiatry, the Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Australia.
4
Department of Human Genetics, National Institute of Mental Health & Neurosciences, Bangalore 560029, India. Electronic address: monozeet@gmail.com.

Abstract

Mitochondria play a critical role in regulating cellular functions including bioenergetics, calcium homeostasis, redox signalling, and apoptotic cell death. Mitochondria are also essential to many aspects of neurodevelopment and neuronal functions. However, mitochondrial impairment may affect bioenergetics in the developing brain and alter critical neuronal processes leading to neurodevelopmental abnormalities. Schizophrenia is a chronic and severe neuropsychiatric disorder of neurodevelopmental origin. Immuno-inflammatory pathway is one of the widely appreciated mechanisms that has consistently been implicated in the neurodevelopmental origin of schizophrenia. However, the source of inflammation and the underlying neurobiological mechanisms leading to schizophrenia are yet to be fully ascertained. Recent understanding reveals that perturbation of mitochondrial network dynamics might lead to various nervous system disorders with inflammatory pathologies. Mitochondrial deficit, altered redox balance and chronic low-grade inflammation are evident in schizophrenia. It is hypothesized that oxidative/nitrosative stress responses due to mitochondrial dysfunctions might activate immuno-inflammatory pathways and subsequently lead to neuroprogressive changes in schizophrenia. Herein, we summarise the current understanding of molecular links between mitochondrial dysfunctions and pathogenesis of schizophrenia based on evidence from genomics, proteomics and imaging studies, which together support a role for mitochondrial impairment in the pathogenetic pathways of schizophrenia.

KEYWORDS:

Inflammation; Mitochondria; Neuroprogression; Oxidative stress; Schizophrenia

PMID:
25446950
DOI:
10.1016/j.neubiorev.2014.11.005
[Indexed for MEDLINE]

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