Mitochondrial complex I subunits expression is altered in schizophrenia: A postmortem study

Rachel Karry, Ehud Klein, Dorit Ben Shachar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)676-684
Number of pages9
JournalBiological Psychiatry
Volume55
Issue number7
DOIs
StatePublished - 1 Apr 2004
Externally publishedYes

Funding

FundersFunder number
Chief Scientist Israel Ministry of Health

    Keywords

    • Mitochondrial complex I
    • Postmortem
    • Prefrontal cortex
    • Schizophrenia
    • Ventral parietooccipital cortex

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