Mitochondrial complex I subunits expression is altered in schizophrenia: a postmortem study.
BACKGROUND
Several independent lines of evidence indicate mitochondrial dysfunction in schizophrenia in the brain and periphery, including mitochondrial hypoplasia, dysfunction of the oxidative phosphorylation system, and altered mitochondrial-related gene expression.


METHODS
In this study, three subunits of mitochondrial complex I were analyzed at the level of mRNA and protein in postmortem brain specimens from the prefrontal and the ventral parietooccipital cortex of patients with schizophrenia, major depression, bipolar disorder, and normal control subjects.


RESULTS
Both mRNA and protein levels of the 24-kDa and 51-kDa subunits of complex I were significantly decreased in the prefrontal cortex, but increased in the ventral parietooccipital cortices of schizophrenia patients compared with normal control subjects. In the latter region, protein levels of both subunits were increased in bipolar patients as well, being in line with the significant overlap in clinical symptoms between schizophrenia and bipolar patients. No change was observed in the 75-kDa subunit expression in the prefrontal cortex.


CONCLUSIONS
The schizophrenia-specific reduction in complex I subunits in the prefrontal cortex is consistent with one of schizophrenia's most prominent deficits, namely, hypofrontality, thus further supporting the hypothesis of mitochondrial dysfunction in this disorder. The abnormal, bidirectional expression of complex I in various brain regions, rather than in a circumscribed area, supports the idea of impaired cerebral circuitry in schizophrenia.
Karry
Rachel
R
Laboratory of Psychobiology, Department of Psychiatry, Rambam Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Klein
Ehud
E
Ben Shachar
Dorit
D
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D003865:Major Depressive Disorder / Q000235:genetics / Q000473:pathology; D042967:Electron Transport Complex I / Q000235:genetics*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D009415:Nerve Net / Q000473:pathology; D009778:Occipital Lobe / Q000473:pathology; D010296:Parietal Lobe / Q000473:pathology; D017397:Prefrontal Cortex / Q000473:pathology; D021122:Protein Subunits / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology
D021122:Protein Subunits; D012333:RNA, Messenger; D042967:Electron Transport Complex I