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Mitochondrial dysfunction in schizophrenia: Pathways, mechanisms and implications.
journal contributionposted on 2015-01-01, 00:00 authored by A Rajasekaran, G Venkatasubramanian, Michael BerkMichael Berk, M Debnath
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.
JournalNeuroscience and Biobehavioral Reviews
Pagination10 - 21
LocationAmsterdam, The Netherlands
Publication classificationC Journal article; C1 Refereed article in a scholarly journal
Copyright notice2014, Elsevier
Read the peer-reviewed publication
InflammationMitochondriaNeuroprogressionOxidative stressSchizophreniaScience & TechnologyLife Sciences & BiomedicineBehavioral SciencesNeurosciencesNeurosciences & NeurologyOXIDATIVE STRESS MARKERSCOMPLEX-I ACTIVITYN-ACETYL CYSTEINEPROGRESSIVE BRAIN CHANGESBLOOD MONONUCLEAR-CELLSBIPOLAR DISORDERNITROSATIVE STRESSCYTOCHROME-CDOUBLE-BLINDPERMEABILITY TRANSITION